Affinage

HBB

Hemoglobin subunit beta · UniProt P68871

Round 2 corrected
Length
147 aa
Mass
16.0 kDa
Annotated
2026-04-28
130 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HBB encodes the beta subunit of adult hemoglobin, the principal oxygen-transport protein in erythrocytes, whose allosteric transition between deoxy (T) and oxy (R) quaternary states is governed by iron displacement from the porphyrin plane and disruption of C-terminal salt bridges upon oxygen binding (PMID:6644819, PMID:6726807). High-level, erythroid-specific transcription requires three proximal promoter elements (CACCC, CCAAT, and TATA boxes) (PMID:3457470), EKLF binding at the CACCC box (PMID:8918890), and long-range chromatin looping between the locus control region (LCR) and the active gene, mediated by cohesin/Nipbl loading and an active chromatin hub whose assembly is accompanied by PRMT1-dependent H4R3 dimethylation, NF-E2-recruited MLL2-catalyzed H3K4 trimethylation, and Ldb1-stabilized P-TEFb recruitment for Pol II elongation (PMID:12504019, PMID:21454523, PMID:20068219, PMID:17707229, PMID:20570862). Post-transcriptionally, splicing is required for nuclear export of beta-globin mRNA, premature termination codons trigger nonsense-mediated decay via hUpf proteins at exon-exon junctions, and transcriptional termination downstream of the poly(A) site proceeds through co-transcriptional cleavage and Xrn2-mediated torpedo degradation (PMID:26362019, PMID:11163187, PMID:15565158). The beta-globin N-terminus undergoes non-enzymatic glycosylation by glucose to form hemoglobin A1c, which accumulates over erythrocyte lifespan and is elevated in diabetes mellitus (PMID:635569).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1975 Medium

    Establishing that beta-globin translation is initiation-limited resolved a basic question about how erythrocytes balance alpha- and beta-chain output, revealing that the two mRNAs compete for limiting initiation factors.

    Evidence Cell-free translation in rabbit reticulocyte lysates with inhibition of alpha-chain synthesis and measurement of elongation vs. initiation rates

    PMID:1125229 PMID:1183442

    Open questions at the time
    • Competition mechanism not defined at the molecular level
    • No identification of the limiting initiation factor(s)
  2. 1976 High

    Identification of the AAUAAA polyadenylation signal in the beta-globin 3′ UTR established a universal cis-element for mRNA 3′ end formation.

    Evidence Direct RNA sequencing of purified human and rabbit beta-globin mRNAs with cross-species comparison

    PMID:822353

    Open questions at the time
    • Trans-acting factors recognizing AAUAAA were not yet identified
  3. 1978 High

    Demonstrating that glucose forms a ketoamine linkage with the HBB N-terminus to produce HbA1c explained a clinically important post-translational modification that accumulates with erythrocyte age and hyperglycemia.

    Evidence Biochemical identification of ketoamine linkage and quantification in normal vs. diabetic red cells

    PMID:635569

    Open questions at the time
    • Structural basis for preferential glycosylation of the beta N-terminus over other hemoglobin residues not resolved
  4. 1980 High

    Complete sequencing of the human beta-globin gene, including two introns and conserved promoter elements (ATA, CCAAT), provided the reference framework for all subsequent mutational and regulatory analyses.

    Evidence DNA sequencing of cloned human beta-globin gene; restriction mapping of delta-beta region

    PMID:6254664 PMID:728996

    Open questions at the time
    • Functional significance of individual promoter elements not yet tested by mutagenesis
  5. 1981 High

    Demonstrating ordered intron removal (small before large) in beta-globin pre-mRNA and conservation of splicing signals across vertebrates established that splicing proceeds through discrete intermediates with a defined pathway.

    Evidence S1 nuclease mapping of rabbit bone marrow RNA identifying partially spliced intermediates; Xenopus microinjection showing cross-species splicing fidelity

    PMID:6946453 PMID:7471214

    Open questions at the time
    • Molecular basis for preferential order of intron removal not determined
  6. 1982 High

    In vitro reconstitution of accurate beta-globin pre-mRNA splicing in HeLa extracts provided a tractable biochemical system and revealed that transcript length and 3′ end position influence splicing efficiency.

    Evidence In vitro splicing with HeLa whole-cell extracts; primer extension verification of splice junctions

    PMID:6292841

    Open questions at the time
    • Specific splicing factors responsible were not identified
  7. 1984 High

    High-resolution crystal structures of oxy- and deoxyhemoglobin revealed the atomic mechanism of the T→R allosteric transition in HBB: iron displacement from the porphyrin plane, haem doming, and loss of C-terminal salt bridges upon oxygenation.

    Evidence X-ray crystallography at 2.1 Å (oxy) and 1.74 Å (deoxy) resolution

    PMID:6644819 PMID:6726807

    Open questions at the time
    • Dynamic pathway of the allosteric transition not captured by static structures
  8. 1986 High

    Saturation mutagenesis defined three essential promoter modules—CACCC, CCAAT, and TATA boxes—resolving which nucleotides within the beta-globin promoter are functionally required for accurate transcription initiation.

    Evidence >100 single-base substitutions tested by transient transfection with SV40 enhancer in HeLa cells

    PMID:3457470

    Open questions at the time
    • Identity of trans-acting factors binding each element not yet established
    • Erythroid-specific activity of these elements not tested here
  9. 1985 High

    Discovery of erythroid-specific LCR hypersensitive sites and demonstration of gene competition for LCR interaction in transgenic mice established the paradigm that distal regulatory elements control developmental switching across the beta-globin locus.

    Evidence Transgenic mice carrying LCR-globin constructs; developmental expression profiling

    PMID:1692558 PMID:2992937

    Open questions at the time
    • Physical mechanism of LCR–gene interaction (looping vs. tracking) unresolved
    • Molecular basis for gene competition not identified
  10. 1988 High

    Showing that premature stop codons at multiple positions reduce beta-globin mRNA levels generalized the phenomenon of nonsense-mediated mRNA reduction beyond individual thalassemia mutations, establishing HBB as a paradigm for NMD.

    Evidence Transfection of five nonsense and two missense HBB mutants; steady-state mRNA quantification

    PMID:3353367

    Open questions at the time
    • Whether the reduction occurs at transcription, nuclear degradation, or cytoplasmic NMD was not yet discriminated
  11. 1992 High

    Dissecting the nuclear component of nonsense-mediated beta-globin mRNA reduction showed that the beta-39 stop codon decreases transcription rate rather than causing cytoplasmic mRNA instability, revealing a previously unrecognized nuclear surveillance mechanism.

    Evidence Nuclear run-on, mRNA stability, and splicing assays in cells with temperature-sensitive RNA Pol II

    PMID:1557399

    Open questions at the time
    • Molecular link between translation termination and transcription rate not identified
    • Relationship to cytoplasmic NMD unclear
  12. 1996 High

    EKLF knockout mice demonstrated that EKLF binding at the CACCC box is essential for beta-globin transcription and for stabilizing LCR–gene interaction, directly linking a specific transcription factor to both chromatin remodeling and gene competition.

    Evidence EKLF−/− mice crossed with human beta-globin locus transgenic mice; allele-specific transcription and chromatin structure analysis

    PMID:8918890

    Open questions at the time
    • How EKLF specificity is achieved in the context of multiple CACCC-containing promoters remained unclear
  13. 2000 High

    Identification of the Xrn2-dependent torpedo mechanism at the beta-globin 3′ flanking region established how RNA Pol II terminates transcription: co-transcriptional cleavage creates a 5′ end that Xrn2 degrades, chasing Pol II off the template.

    Evidence RNAi knockdown of Xrn2 in HeLa cells; nuclear run-on; characterization of CoTC RNA

    PMID:15565158

    Open questions at the time
    • How CoTC autocatalytic cleavage is regulated in vivo not determined
  14. 2000 High

    Demonstrating that human Upf proteins associate with spliced beta-globin mRNA at exon-exon junctions and that tethering any hUpf to the 3′ UTR elicits NMD identified the cytoplasmic arm of quality control acting on premature-stop beta-globin transcripts.

    Evidence Co-immunoprecipitation; tethering assay with beta-globin 3′ UTR reporters; subcellular localization

    PMID:11163187

    Open questions at the time
    • Relative contributions of nuclear mRNA reduction vs. cytoplasmic NMD for beta-globin transcripts not quantified
  15. 2002 High

    Chromosome conformation capture demonstrated that the LCR and active beta-globin genes form a looped chromatin hub in erythroid cells (but not brain), physically resolving the long-standing question of how a distal enhancer contacts its target gene.

    Evidence 3C assay across ~200 kb of mouse beta-globin locus in erythroid vs. brain tissue

    PMID:12504019 PMID:14517543

    Open questions at the time
    • Factors mediating loop formation not yet identified
    • Temporal order of hub assembly relative to transcription not established
  16. 2007 High

    Identification of NF-E2-dependent recruitment of MLL2 for H3K4 trimethylation and HS2-dependent intergenic Pol II recruitment resolved how activator-directed histone methylation spreads across the beta-globin locus and distinguished intergenic from genic transcription complexes.

    Evidence Co-IP plus mass spectrometry of MLL2-NF-E2; ChIP during erythroid differentiation; HS2 and TATA box mutations in minichromosome

    PMID:17283048 PMID:17707229

    Open questions at the time
    • Whether MLL2 spreading requires intergenic transcription was not determined
  17. 2010 High

    PRMT1-catalyzed H4R3 dimethylation was shown to be an upstream prerequisite for H3 acetylation and LCR–promoter looping, while Ldb1 was shown to stabilize the erythroid transcription complex and recruit P-TEFb for Pol II elongation, ordering the epigenetic cascade that activates beta-globin.

    Evidence PRMT1 RNAi/rescue with ChIP, 3C, and in vitro acetylation; Ldb1 knockdown with ChIP for P-TEFb and FISH for nuclear relocalization

    PMID:20068219 PMID:20570862

    Open questions at the time
    • Whether H4R3me2 is sufficient or merely necessary for H3 acetylation in vivo not tested
    • Mechanism by which Ldb1 promotes nuclear migration is unknown
  18. 2011 High

    Showing that cohesin and Nipbl bind the LCR, CTCF insulators, and active globin genes upon differentiation, and that Nipbl is required for long-range interactions, identified the structural machinery mediating the chromatin loops essential for beta-globin expression.

    Evidence ChIP for cohesin/Nipbl during differentiation; 3C; Nipbl heterozygous mouse model

    PMID:21454523

    Open questions at the time
    • Whether cohesin actively extrudes loops or passively stabilizes them at the beta-globin locus is unknown
  19. 2020 High

    CRISPR knockout of HBB revealed an ATF4–MYB–BCL11A stress pathway that reactivates gamma-globin, establishing a feedback circuit by which loss of beta-globin induces compensatory fetal hemoglobin expression.

    Evidence CRISPR-Cas9 HBB knockout in isogenic erythroid precursors; RNA-seq; ChIP-seq for ATF4

    PMID:32755585

    Open questions at the time
    • Whether ATF4 activation reflects translational stress, heme excess, or another signal is not resolved
    • Applicability to heterozygous beta-thalassemia not tested
  20. 2023 Medium

    Discovery that HBB protein localizes to mitochondria and suppresses ROS via NDUFAF5, scaffolded by lncRNA16, revealed an unexpected extrahematopoietic function linked to chemoresistance in lung cancer.

    Evidence ChIRP-MS; RIP; RNA pull-down; GalNAc-siRNA in mouse chemoresistance models

    PMID:38155279

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Mechanism by which HBB–NDUFAF5 interaction suppresses ROS is undefined
    • Physiological relevance of mitochondrial HBB outside cancer unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanistic basis for how the beta-globin locus integrates chromatin looping, histone modification cascades, and transcription factor competition to achieve precise developmental switching from gamma- to beta-globin remains incompletely understood at single-molecule resolution.
  • No real-time single-molecule imaging of LCR–gene loop dynamics in living erythroid cells
  • Quantitative contribution of each epigenetic mark (H3K4me3, H4R3me2a, H3ac) to transcriptional output not individually titrated
  • Structural basis for EKLF selectivity toward the beta-globin promoter context beyond the CACCC sequence remains unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0140104 molecular carrier activity 2
Localization
GO:0005829 cytosol 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-4839726 Chromatin organization 6 R-HSA-8953854 Metabolism of RNA 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-382551 Transport of small molecules 2 R-HSA-392499 Metabolism of proteins 2
Partners
EKLFGATA1HBA1LDB1MLL2NDUFAF5NIPBLXRN2
Complex memberships
Active Chromatin Hub (LCR-globin gene cluster)Hemoglobin (alpha2-beta2 tetramer)

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1975 The beta subunit of hemoglobin (HBB) is translated from its mRNA by ribosomes; when alpha-globin synthesis is inhibited, beta-globin synthesis is stimulated, with the rate of elongation increasing more than initiation, indicating that initiation is the rate-limiting step in beta-globin production and that alpha and beta mRNAs compete for limiting translation components. Cell-free translation assay with rabbit reticulocytes; inhibition of alpha-chain synthesis with O-methyl-L-threonine; radioactive amino acid incorporation; carboxymethyl cellulose chromatography; SDS-PAGE; tryptic peptide electrophoresis European journal of biochemistry Medium 1183442
1975 Alpha- and beta-globin mRNAs are translated with equivalent fidelity and efficiency; proteins associated with polysomal mRNA (mRNP) do not alter the specificity of translation or the requirement for initiation factors, as shown by identical products and efficiencies from mRNP and deproteinized mRNA. Cell-free translation of rabbit reticulocyte mRNP and deproteinized mRNA in mouse Krebs II ascites tumor cell system; comparison with and without reticulocyte initiation factors Biochimica et biophysica acta Medium 1125229
1976 The hexanucleotide sequence AAUAAA is present ~20 residues upstream of the 3'-terminal poly(A) in beta-globin mRNA (and other eukaryotic mRNAs), identifying this as a conserved polyadenylation signal in the 3' non-coding region of HBB mRNA. RNA sequencing of purified alpha- and beta-globin mRNAs from rabbit and human; sequence comparison across six eukaryotic mRNAs Nature High 822353
1978 Glucose reacts nonenzymatically with the NH2-terminal amino acid of the beta chain of human hemoglobin (HBB) via a ketoamine linkage, forming hemoglobin A1c; this glycosylation accumulates throughout the 120-day erythrocyte lifespan and is elevated two- to threefold in diabetic patients. Biochemical characterization of hemoglobin A1c; identification of ketoamine linkage; measurement in normal and diabetic red cells Science High 635569
1979 A splicing region (~500 bp SV40 segment) is required for accumulation of stable beta-globin mRNA in infected monkey cells; without this splicing sequence, a beta-globin recombinant retains the late region promoter but produces neither stable globin transcript nor detectable beta-globin protein. SV40-rabbit beta-globin recombinant virus construction; transfection into monkey cells; RNA stability analysis; radioimmunoassay for beta-globin protein Cell High 225043
1980 The human beta-globin gene contains two intervening sequences (introns): a small one near the 5' end and a large one (~900 bp) between codons for amino acids 104 and 105; the linked delta-globin gene has a large intervening sequence at the identical coding position but with little sequence homology to the beta-globin intron. Molecular cloning from bacteriophage lambda libraries; restriction endonuclease mapping; partial DNA sequencing; hybridization experiments Cell High 728996
1980 The complete nucleotide sequence of the human beta-globin gene was determined, including the promoter regions with conserved ATA (~-31 bp) and CCAAT (~-77 bp) sequences upstream of the transcription start site, providing the basis for comparing normal and mutant beta-globin genes. DNA sequencing of cloned human beta-globin gene Cell High 6254664
1981 The rabbit beta-globin gene produces a colinear pre-mRNA transcript whose 5' and 3' ends map at the same positions as mature mRNA; splicing proceeds via partially spliced intermediates, with the small intervening sequence removed before the large one, demonstrating stepwise splicing of both introns. S1 nuclease mapping of RNA from rabbit bone marrow; characterization of splicing intermediates Cell High 7471214
1981 The rabbit beta-globin promoter is recognized in Xenopus frog embryos and transcripts are correctly spliced, demonstrating conservation of beta-globin transcription and splicing signals across vertebrates. Microinjection of rabbit beta-globin gene into fertilized Xenopus eggs; S1 nuclease mapping of transcripts Proceedings of the National Academy of Sciences of the United States of America Medium 6946453
1982 Human beta-globin pre-mRNA is accurately spliced in vitro by HeLa whole-cell extracts; the small intervening sequence is removed with correct junction sequence; transcripts terminated upstream of the polyadenylation site are spliced most efficiently, while transcripts terminated downstream are not spliced at all. In vitro splicing with HeLa whole-cell extracts; primer extension analysis of splice junctions; comparison of transcripts with different termination points Nucleic acids research High 6292841
1983 Beta-globin gene expression is induced 5- to 50-fold upon chemical differentiation of murine erythroleukemia (MEL) cells, with nuclear transcription experiments showing increased transcription rate; the induction is specific to globin genes in an erythroid cell context, and regulatory sequences are conserved between mouse and human. Stable transfection of MEL cells; S1 nuclease and primer extension analysis; nuclear transcription run-on assay; chemical induction of differentiation Cell High 6572107
1983 The structure of human oxyhaemoglobin was determined at 2.1 Å resolution; the beta subunit HBB iron atom lies 0.00(8) Å from the porphyrin mean plane in the oxy state; the haem is ruffled in the beta subunit; the Fe-O(1) bond length is 1.87(13) Å; HisE7 forms no hydrogen bond (or only weak) to the oxygen in the beta subunit, in contrast to the alpha subunit; C-terminal HisHC3(146 beta) is delocalized and cannot form the intersubunit salt bridges present in deoxyhaemoglobin. Single crystal X-ray crystallography at 2.1 Å resolution; Jack-Levitt refinement Journal of molecular biology High 6644819
1984 The structure of human deoxyhaemoglobin was refined at 1.74 Å resolution; in the beta haem, the iron is displaced 0.36(5) Å from the porphyrin nitrogen mean plane toward the proximal histidine; the Fe-Nepsilon(F8) bond is 2.12(4) Å; beta haem shows no uniform tilting of pyrrole planes but pyrroles II and IV (eclipsed by His F8) are tilted ~8°; the haem is domed toward the proximal side, consistent with the allosteric T-state mechanism. Synchrotron X-ray crystallography at 1.74 Å; crystallographic refinement (R=16.0%) Journal of molecular biology High 6726807
1984 The modular promoter structure of the beta-globin gene was defined: elements from the beta-globin ATA box, middle element, and distal element can be functionally exchanged with corresponding elements from the TK promoter; the beta-globin ATA box is required for full activity, as mosaic promoters retaining it are equally active to the wild-type promoter, while those with TK ATA box are 4–10 fold less active. Construction of mosaic beta-globin/TK promoters; enhancer-dependent transient expression assay in cell culture The EMBO journal Medium 6096121
1985 Erythroid-specific DNase I super-hypersensitive (HS) sites upstream of the human beta-globin locus (the locus control region, LCR) are required for high-level expression of beta-globin genes in transgenic mice; when HS sequences were combined with both gamma- and beta-globin gene fragments, correct developmental switching was restored, suggesting competition among globin genes for interaction with the HS sequences. Transgenic mouse experiments; microinjection of constructs containing HS sites fused to individual or combined globin genes; measurement of globin expression and developmental regulation Genes & development High 1692558
1985 A thalassemia mutation (IVS2-705) causes beta-globin pre-mRNA missplicing via two aberrant splices in the large intron; introduction of a second mutation into the cryptic 3' splice site at position 580 completely reverses the aberrant splicing and restores normal IVS2 removal, demonstrating that the two abnormal splice events are subtly interdependent. Expression of cloned thalassemia beta-globin gene in HeLa cells; oligomer-directed mutagenesis of cryptic splice site; RNA analysis The Journal of biological chemistry High 3840804
1985 Human beta-globin genes introduced into transgenic mice with up to 4300 bp of 5'-flanking sequence are expressed in an erythroid-specific manner at levels comparable to endogenous mouse beta-globin; expression is first detected between days 11–14 of development; constructs with as little as 48 bp of 5'-flanking sequence are also expressed appropriately, and the mRNA directs beta-globin protein synthesis in reticulocyte lysates. Transgenic mouse production by microinjection; Northern blot and S1 analysis of beta-globin mRNA; reticulocyte lysate in vitro translation; protein detection in mature erythrocytes The EMBO journal High 2992937
1985 Sequences 0.5–1.2 kb downstream from the beta-globin poly(A) addition site constitute a transcriptional enhancer element that is erythroid- and developmental stage-specific, demonstrating that the human beta-globin gene contains a downstream cis-regulatory element contributing to its regulated expression. Transgenic mouse experiments with constructs containing downstream deletions; reporter gene assays in tissue culture Nucleic acids research Medium 3039464
1986 Saturation mutagenesis of the mouse beta-major globin promoter defined three cis-acting regions required for accurate and efficient transcription initiation: (i) the CACCC box (-87 to -95), (ii) the CCAAT box (-72 to -77), and (iii) the TATA box (-26 to -30); mutations in other regions had no effect, while two mutations immediately upstream of the CCAAT box increased transcription 3- to 3.5-fold. Saturation mutagenesis (>100 single base substitutions); transient transfection into HeLa cells with SV40 enhancer; measurement of correctly initiated beta-globin transcripts Science High 3457470
1988 Nonsense mutations at multiple positions in the human beta-globin gene decrease the steady-state level of beta-globin mRNA in a transfection system; this effect is a general property of premature translation termination codons in beta-globin, not restricted to specific codons or types of nonsense mutations. Heterologous transfection of cloned beta-globin genes with five nonsense and two missense mutations; measurement of beta-globin mRNA steady-state levels Proceedings of the National Academy of Sciences of the United States of America High 3353367
1988 The chicken beta-globin enhancer stimulates transcription of both beta- and epsilon-globin genes; developmental stage-specific regulation of beta-globin requires interaction between the enhancer and a positive regulatory element (stage selector element, SSE) within the adult beta-globin promoter, as defined by deletion and substitution analysis. Deletion and substitution mutant analysis of chicken beta-globin enhancer and promoter elements; transient transfection assays in erythroid cells Cell High 3167976
1989 Transcriptionally active extracts from chick red cells support beta-globin transcription in vitro; two proteins—PAL (a repressor, highest in mature red cells) and CON (an activator, highest in actively transcribing cells)—bind adjacent sites in the beta-globin promoter and have opposing effects on transcription; PAL's repression can be overcome by blocking its binding site with a protein with similar recognition sequence but different function. In vitro transcription with erythroid cell extracts at different developmental stages; identification of PAL and CON by DNA binding and functional assays Cell High 2736626
1992 The beta-39 nonsense mutation causes deficient accumulation of beta-globin mRNA through a defect occurring prior to mRNA accumulation in the cytoplasm (i.e., in the nucleus); mRNA cytoplasmic stability, 3' end processing, and splicing accuracy are normal, and reduced transcription rate fully or partially accounts for the decreased mRNA, suggesting a nuclear/transcriptional mechanism for nonsense-mediated mRNA reduction. Transfection into cell lines with temperature-sensitive RNA Pol II; nuclear run-on transcription; mRNA stability analysis; splicing and polyadenylation assays Proceedings of the National Academy of Sciences of the United States of America High 1557399
1993 The human beta-globin gene domain contains a single bidirectional replication origin located immediately upstream of the beta-globin gene; this origin is used for DNA synthesis initiation in both expressing and non-expressing cells (which differ in replication timing). Deletion of this origin (as in hemoglobin Lepore syndrome) cancels bidirectional synthesis and reverses replication direction, providing genetic proof of a discrete mammalian replication origin. Replication direction assay on >200 kb of the human beta-like globin domain; analysis of hemoglobin Lepore deletion patients Nature High 8255298
1996 EKLF (erythroid Krüppel-like factor) binds the beta-globin CACCC box and stabilizes the interaction between the LCR and the beta-globin gene; in EKLF knockout mice, beta-globin transcription is absent with concurrent chromatin structure changes at the beta promoter, and the gamma/beta gene competition ratio is altered, demonstrating EKLF's role in gene competition within the locus. EKLF knockout/human beta-locus transgenic compound mice; allele-specific transcription analysis; chromatin structure analysis at beta and gamma promoters Genes & development High 8918890
1997 Novel intergenic nuclear transcripts span the LCR and intergenic regions of the human beta-globin locus in erythroid cells; transfection of a beta-globin gene (epsilon, gamma, or beta) induces transcription of the LCR and intergenic regions from the chromosomal locus in nonerythroid cells (transinduction), dependent on transcription of the plasmid-borne globin gene but not protein expression; in situ hybridization shows the plasmid colocalizes with the endogenous locus. Nuclear run-on analysis; in situ hybridization; transient transfection in nonerythroid cells; colocalization experiments Genes & development High 9334315
1998 EKLF activates the beta-globin promoter through the overall structure of the beta promoter rather than solely through the CACCC box sequence; swapping CACCC boxes between beta and gamma promoters shows that EKLF's specificity is determined by the promoter context, not just the CACCC sequence or its position. Transient transfection assays in CV-1 and K562 cells; chimeric beta/gamma promoter constructs with swapped CACCC boxes; EKLF co-transfection Molecular and cellular biology Medium 9418858
1998 Trans-splicing group I ribozymes convert sickle beta-globin transcripts into mRNAs encoding anti-sickling gamma-globin in erythrocyte precursors derived from sickle cell disease patients, demonstrating that RNA repair via trans-splicing can alter beta-globin mRNA in primary human cells. Group I ribozyme trans-splicing in erythrocyte precursors from sickle cell patients; RT-PCR and sequencing of repaired transcripts Science Medium 9616120
2000 Human 5'→3' exonuclease Xrn2 promotes transcriptional termination of the beta-globin gene downstream of the poly(A) signal; co-transcriptional cleavage (CoTC) ~1 kb downstream creates a free 5' RNA end that is degraded by Xrn2, and this degradation induces dissociation of RNA Pol II from the template (torpedo model of termination). RNA interference knockdown of Xrn2 in HeLa cells; nuclear run-on assays; analysis of co-transcriptional cleavage activity; characterization of CoTC as autocatalytic RNA structure Nature High 15565158
2001 BP1, a homeodomain protein and isoform of DLX4, binds two silencer sequences upstream of the adult human beta-globin gene and represses beta-globin promoter activity in cotransfection assays; BP1 expression decreases upon induction of the beta-globin gene in erythroid cells, and mutation of the -150 CAGTGC binding motif abolishes both BP1 binding and its repressive function. cDNA cloning and sequencing; cotransfection assays with beta-globin promoter reporter; gel-shift competition assays; mutagenesis of binding sites Molecular and cellular biology Medium 11909945
2001 Nuclear ferritin (ferritin-H enriched) binds specifically to a CAGTGC motif at -153 to -148 bp in the beta-globin promoter; purified ferritin-H and expressed ferritin-H repress beta-globin promoter-driven reporter expression in cotransfected cells when EKLF is present as activator; mutation of the CAGTGC motif reduces binding 20-fold and abrogates ferritin-H repression while retaining EKLF activation. Gel-shift/competition assays with K562 nuclear extracts; cotransfection of ferritin-H expression clones with CAT reporter; mutagenesis of CAGTGC motif Proceedings of the National Academy of Sciences of the United States of America Medium 11481480
2002 In erythroid cells, the LCR hypersensitive sites come into close spatial proximity with the active beta-globin genes, with intervening chromatin (containing inactive genes) looping out; in non-expressing brain tissue, the locus adopts a linear conformation; distant HS regions also participate in these interactions, demonstrating that spatial clustering of regulatory elements creates active chromatin domains. Chromosome conformation capture (3C) assay; formaldehyde crosslinking in erythroid and brain cells; analysis of ~200 kb of murine beta-globin locus Molecular cell High 12504019
2003 The active chromatin hub (ACH) of the beta-globin locus is developmentally conserved in mice and humans, consisting of LCR HS1-6, upstream 5'HS-60/-62 and 3'HS1; individual globin genes switch their interaction with this core cluster correlating with their transcriptional activity; in committed but not yet expressing erythroid progenitors, only a subset of interactions are stable, and full hub assembly occurs upon differentiation-triggered gene activation. 3C analysis at multiple developmental stages; comparison of mouse and human loci; analysis in erythroid progenitors and differentiated cells Nature genetics High 14517543
2004 Mutations in the 5'UTR of the human beta-globin gene (+10, +22, +33, +40-43) reduce steady-state mRNA to 61–86% of wild-type; nuclear run-on experiments show that mutations +10 and +33 reduce transcription rate, accounting for decreased mRNA, while +22 acts post-transcriptionally; none affect mRNA transport, 3' end processing, or stability. Stable transfection of mutant HBB genes in MEL cells with LCR; Northern blot; nuclear run-on; mRNA stability and transport assays British journal of haematology High 15009072
2004 In adult murine erythroid cells, the LCR and transcribed beta-globin genes exist within domains of histone acetylation with RNA Pol II; silent embryonic genes lie in hypoacetylated chromatin without Pol II; in human K562 cells, H3/H4 acetylation and H3K4 methylation are continuous over 17 kb including LCR and active epsilon-globin gene, varying directly with transcription, while HeLa cells show H3K9 methylation instead. Chromatin immunoprecipitation (ChIP) with real-time PCR; analysis of histone modifications and Pol II across globin locus Proceedings of the National Academy of Sciences of the United States of America High 15105444
2007 The MLL2 histone methyltransferase complex associates with the hematopoietic activator NF-E2 in erythroid cells; NF-E2-dependent recruitment of MLL2 to the beta-globin locus is required for H3K4 trimethylation and maximal transcription; MLL2-associated subunit ASH2L is restricted to the LCR while MLL2 itself spreads across the entire beta-globin locus, revealing a mechanism for activator-directed H3K4 methylation at a distance. Co-immunoprecipitation of MLL2 complex with NF-E2; ChIP during erythroid differentiation; NF-E2 knockdown; mass spectrometry identification of complex components Molecular cell High 17707229
2007 Beta-globin intergenic transcription and histone H3 acetylation/K4 methylation in sequences between HS2 and the epsilon-globin gene require an intact HS2 enhancer that recruits RNA Pol II; Pol II recruitment at HS2 and intergenic modifications are not sufficient for target gene transcription, which additionally requires initiation at the gene's own TATA box, demonstrating that intergenic and genic transcription complexes are independent. Minichromosome system with HS2-epsilon-globin; ChIP for Pol II and histone modifications; TATA box mutations; HS2 enhancer mutations Molecular and cellular biology High 17283048
2008 GATA-1 binding at LCR HS2 directly recruits CBP histone acetyltransferase and RNA Pol II to HS2; loss of GATA-1 at HS2 severely reduces epsilon-globin transcription with loss of Pol II from the transcription start site and reduction of H3 acetylation and H3K4 di/tri-methylation in coding sequences, while H3K4 mono-methylation remains unaffected. Minichromosome with mutated GATA-1 sites in HS2; ChIP for CBP, Pol II, and histone modifications; RNAi knockdown of NF-E2; DNase I hypersensitivity assay Nucleic acids research High 18586828
2010 PRMT1-mediated asymmetric dimethylation of H4R3 at the beta-globin locus facilitates histone H3 acetylation on Lys9/Lys14 by providing a binding surface for PCAF; dimethyl H4R3 directly enhances H3 acetylation in vitro; PRMT1 knockdown prevents H3 acetylation, LCR-promoter interaction, and recruitment of transcription preinitiation complexes, blocking beta-globin transcription and erythroid differentiation. PRMT1 RNAi knockdown and rescue with rat PRMT1; ChIP for H4R3me2 and H3 acetylation; in vitro acetylation assay; 3C for LCR-promoter interaction; Pol II ChIP Blood High 20068219
2010 Ldb1 stabilizes its erythroid partners (SCL, GATA-1, LMO2) on beta-globin chromatin and is required for enrichment of P-TEFb (which phosphorylates Ser2 of RNA Pol II CTD for elongation); Ldb1 reduction prevents locus migration from the nuclear periphery to transcription factories, implicating nuclear relocalization as a critical step for robust beta-globin transcription. Ldb1 knockdown; ChIP for erythroid complex components and P-TEFb; nuclear localization by FISH; differentiation assays Blood High 20570862
2011 Upon erythroid differentiation, cohesin and its loading factor Nipbl bind the beta-globin LCR, CTCF insulator elements, and the specific activated globin gene; Nipbl-dependent cohesin binding is required for long-range chromatin interactions between CTCF insulators and between the LCR distal enhancer and the target gene, and these interactions are necessary for globin gene expression. ChIP for cohesin and Nipbl during differentiation; 3C for chromatin interactions; Nipbl heterozygous mouse model; loss-of-function assays in cell culture The Journal of biological chemistry High 21454523
2015 Splicing promotes the nuclear export of beta-globin mRNA by overcoming an active nuclear retention element present in the mRNA; unspliced cDNA-derived beta-globin mRNA is retained in the nucleus and degraded, and this retention can be overcome by increasing mRNA length or by splicing, indicating a default export pathway opposed by specific nuclear retention sequences in HBB mRNA. Reporter constructs with beta-globin sequences in HeLa cells; nuclear/cytoplasmic fractionation; analysis of spliced vs. intronless beta-globin mRNA; length-dependence experiments RNA Medium 26362019
2016 The beta subunit of hemoglobin (HBB) acts as a lung-derived antimetastatic factor; a C-terminal peptide (Metox) mediates growth arrest and apoptosis of neuroblastoma and other cancer cell lines; HBB2 is produced by alveolar epithelial and endothelial cells in mice and is upregulated in mice bearing clinically undetectable metastasis. Peptide mapping; in vitro cell viability and apoptosis assays; in vivo xenograft and spontaneous metastasis mouse models; expression studies by immunohistochemistry and ELISA Cancer research Medium 27793844
2020 Decreased beta-globin expression (modeled by CRISPR-Cas9 knockout) induces robust re-expression of gamma-globin in differentiating erythroid precursors; ATF4 binds within the HBS1L-MYB intergenic enhancer to regulate MYB expression; reduced ATF4 upon beta-globin knockout decreases MYB and BCL11A levels, identifying ATF4 as a regulator of stress-induced gamma-globin compensation. CRISPR-Cas9 knockout of HBB in isogenic erythroid precursors; RNA-seq; ChIP-seq for ATF4 binding; functional knockdown of ATF4 Cell reports High 32755585
2023 LncRNA16 binds to HBB protein and promotes HBB accumulation by inhibiting autophagy; lncRNA16 functions as a scaffold facilitating colocalization of HBB and NDUFAF5 in mitochondria; HBB/NDUFAF5 axis inhibits ROS generation, and this pathway contributes to chemoresistance in non-small cell lung cancer. ChIRP-MS (comprehensive identification of RNA-binding proteins by mass spectrometry); RNA immunoprecipitation (RIP); RNA pull-down; immunohistochemistry; mouse chemoresistance models; GalNAc-siRNA targeting Science China. Life sciences Medium 38155279
2000 Human Upf proteins (hUpf1, hUpf2, hUpf3a, hUpf3b) are required for nonsense-mediated decay (NMD) of beta-globin mRNA containing premature termination codons; hUpf3a and hUpf3b associate selectively with spliced beta-globin mRNA in vivo, and tethering any hUpf protein to the 3'UTR of beta-globin mRNA elicits NMD, establishing that exon-exon junctions downstream of a termination codon mark mRNA for decay. Co-immunoprecipitation; tethering assay with beta-globin mRNA 3'UTR reporters; subcellular localization by microscopy; in vivo mRNA association assays Cell High 11163187

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
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2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
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2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2006 Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Molecular cell 1260 16916647
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2002 Looping and interaction between hypersensitive sites in the active beta-globin locus. Molecular cell 1054 12504019
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1982 Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature 939 6280057
1978 The glycosylation of hemoglobin: relevance to diabetes mellitus. Science (New York, N.Y.) 888 635569
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2009 Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans. Proceedings of the National Academy of Sciences of the United States of America 702 19372376
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
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2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1985 The "beta-like-globin" gene domain in human erythroid cells. Proceedings of the National Academy of Sciences of the United States of America 576 3879975
2008 Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proceedings of the National Academy of Sciences of the United States of America 544 18245381
1983 Structure of human oxyhaemoglobin at 2.1 A resolution. Journal of molecular biology 505 6644819
1980 The nucleotide sequence of the human beta-globin gene. Cell 490 6254664
2000 Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell 484 11163187
1989 A review of the molecular genetics of the human alpha-globin gene cluster. Blood 479 2649166
2008 DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proceedings of the National Academy of Sciences of the United States of America 454 18667698
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1984 Nonuniform recombination within the human beta-globin gene cluster. American journal of human genetics 428 6097112
1980 Molecular cloning and characterization of the human beta-like globin gene cluster. Cell 421 6155216
2002 Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet (London, England) 417 11965279
2004 Human 5' --> 3' exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites. Nature 389 15565158
1975 Three-dimensional fourier synthesis of human deoxyhaemoglobin at 2-5 A resolution: refinement of the atomic model. Journal of molecular biology 387 1177322
1985 Erythroid-specific expression of human beta-globin genes in transgenic mice. The EMBO journal 367 2992937
1997 Characterization of the chicken beta-globin insulator. Proceedings of the National Academy of Sciences of the United States of America 319 9012826
1988 Developmental regulation of beta-globin gene switching. Cell 308 3167976
1997 Intergenic transcription and transinduction of the human beta-globin locus. Genes & development 289 9334315
1990 Human gamma- to beta-globin gene switching in transgenic mice. Genes & development 263 1692558
1981 Isolation of beta-globin-related genes from a human cosmid library. Gene 257 6266915
1988 Nonsense mutations in the human beta-globin gene affect mRNA metabolism. Proceedings of the National Academy of Sciences of the United States of America 249 3353367
1993 Replication structure of the human beta-globin gene domain. Nature 247 8255298
1996 The role of EKLF in human beta-globin gene competition. Genes & development 180 8918890
1998 Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors. Science (New York, N.Y.) 174 9616120
1983 The regulated expression of beta-globin genes introduced into mouse erythroleukemia cells. Cell 159 6572107
2012 Reawakening fetal hemoglobin: prospects for new therapies for the β-globin disorders. Blood 147 22904296
1987 The human beta-globin gene contains a downstream developmental specific enhancer. Nucleic acids research 142 3039464
1981 Transformation of frog embryos with a rabbit beta-globin gene. Proceedings of the National Academy of Sciences of the United States of America 129 6946453
1979 SV40 recombinants carrying rabbit beta-globin gene coding sequences. Cell 125 225043
1992 Beta-globin nonsense mutation: deficient accumulation of mRNA occurs despite normal cytoplasmic stability. Proceedings of the National Academy of Sciences of the United States of America 124 1557399
1987 Association of thalassaemia intermedia with a beta-globin gene haplotype. British journal of haematology 114 2436649
2007 Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locus. Molecular cell 108 17707229
2008 Beta-globin regulation and long-range interactions. Advances in genetics 99 18282504
1984 Evolution of the mammalian beta-globin gene cluster. The Journal of biological chemistry 87 6706976
2010 H4R3 methylation facilitates beta-globin transcription by regulating histone acetyltransferase binding and H3 acetylation. Blood 86 20068219
2002 ChIPs of the beta-globin locus: unraveling gene regulation within an active domain. Current opinion in genetics & development 82 11893490
2011 Cohesin mediates chromatin interactions that regulate mammalian β-globin expression. The Journal of biological chemistry 81 21454523
1997 Characterization of adult alpha- and beta-globin genes in the zebrafish. Blood 76 9002973
1989 Erythroid-specific activation and derepression of the chick beta-globin promoter in vitro. Cell 74 2736626
1990 Beta-globin locus activation regions: conservation of organization, structure, and function. Proceedings of the National Academy of Sciences of the United States of America 72 2236034
1984 Localization of the beta-globin gene by chromosomal in situ hybridization. American journal of human genetics 72 6587773
2008 Joining the loops: beta-globin gene regulation. IUBMB life 71 18767169
1998 A common human beta globin splicing mutation modeled in mice. Blood 71 9490703
1982 Accurate in vitro splicing of human beta-globin RNA. Nucleic acids research 68 6292841
2010 Multiple functions of Ldb1 required for beta-globin activation during erythroid differentiation. Blood 67 20570862
1993 Regulation of the beta-globin locus. Current opinion in genetics & development 67 8504248
1978 Variability in the amount of beta-globin mRNA in beta0 thalassemia. Cell 65 667942
1976 Presence of gene for beta globin in homozygous beta0 thalassaemia. Nature 64 1246358
2013 Chronic inflammatory state in sickle cell anemia patients is associated with HBB(*)S haplotype. Cytokine 58 24290434
2004 Developmental stage differences in chromatin subdomains of the beta-globin locus. Proceedings of the National Academy of Sciences of the United States of America 57 15105444
1998 Recombination breakpoints in the human beta-globin gene cluster. Blood 57 9834248
2008 Epigenetics of beta-globin gene regulation. Mutation research 56 18760288
2002 Reliability of DHPLC in mutational screening of beta-globin (HBB) alleles. Human mutation 52 11857746
1985 Analysis of an inversion within the human beta globin gene cluster. Nucleic acids research 52 4000967
2018 Gene correction of HBB mutations in CD34+ hematopoietic stem cells using Cas9 mRNA and ssODN donors. Molecular and cellular pediatrics 46 30430274
1981 A transcription map for the rabbit beta-globin gene. Cell 45 7471214
2002 BP1, a homeodomain-containing isoform of DLX4, represses the beta-globin gene. Molecular and cellular biology 44 11909945
2009 Rapid identification of HBB gene mutations by high-resolution melting analysis. Clinical biochemistry 42 19631632
2000 Activation of the beta globin locus by transcription factors and chromatin modifiers. The EMBO journal 39 10990462
2016 The Beta Subunit of Hemoglobin (HBB2/HBB) Suppresses Neuroblastoma Growth and Metastasis. Cancer research 38 27793844
2008 The role of transcriptional activator GATA-1 at human beta-globin HS2. Nucleic acids research 38 18586828
2001 An orphaned mammalian beta-globin gene of ancient evolutionary origin. Proceedings of the National Academy of Sciences of the United States of America 38 11158601
2007 Beta-globin intergenic transcription and histone acetylation dependent on an enhancer. Molecular and cellular biology 37 17283048
1998 Activation of beta-globin promoter by erythroid Krüppel-like factor. Molecular and cellular biology 35 9418858
2020 ATF4 Regulates MYB to Increase γ-Globin in Response to Loss of β-Globin. Cell reports 33 32755585
2015 Trans-spliced Cas9 allows cleavage of HBB and CCR5 genes in human cells using compact expression cassettes. Scientific reports 33 26126518
2005 Genomic imprinting recapitulated in the human beta-globin locus. Proceedings of the National Academy of Sciences of the United States of America 33 16006531
1975 Synthesis of alpha- and beta-globin directed by messenger ribonucleoprotein from rabbit reticulocytes. Biochimica et biophysica acta 33 1125229
1992 A beta-thalassaemia phenotype not linked to the beta-globin cluster in an Italian family. British journal of haematology 32 1643026
2017 A phased SNP-based classification of sickle cell anemia HBB haplotypes. BMC genomics 30 28800727
2001 Specific repression of beta-globin promoter activity by nuclear ferritin. Proceedings of the National Academy of Sciences of the United States of America 30 11481480
2007 Protection against telomeric position effects by the chicken cHS4 beta-globin insulator. Proceedings of the National Academy of Sciences of the United States of America 29 17715059
2007 Control of beta globin genes. Journal of cellular biochemistry 29 17910027
1985 Structure and organization of the bovine beta-globin genes. Molecular biology and evolution 29 3870874
2004 Thalassaemia mutations within the 5'UTR of the human beta-globin gene disrupt transcription. British journal of haematology 28 15009072
1999 Oxygen tension modulates beta-globin switching in embryoid bodies. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 9973316
1985 Reversibility of IVS 2 missplicing in a mutant human beta-globin gene. The Journal of biological chemistry 27 3840804
1982 Gene evolution in the chicken beta-globin cluster. Cell 27 6896168
2017 Investigation of mutations in the HBB gene using the 1,000 genomes database. PloS one 26 28379995
2006 African gene flow to north Brazil as revealed by HBB*S gene haplotype analysis. American journal of human biology : the official journal of the Human Biology Council 26 16378338
2015 Splicing promotes the nuclear export of β-globin mRNA by overcoming nuclear retention elements. RNA (New York, N.Y.) 25 26362019
1997 Incorporation of beta-globin untranslated regions into a Sindbis virus vector for augmentation of heterologous mRNA expression. Gene therapy 25 9231080
1984 Modular structure of the beta-globin and the TK promoters. The EMBO journal 24 6096121
1975 Interaction between the synthesis of alpha and beta globin. European journal of biochemistry 22 1183442
2005 Developmental regulation of the beta-globin gene locus. Progress in molecular and subcellular biology 21 15881896
2002 Temperature-dependent splicing of beta-globin pre-mRNA. Nucleic acids research 21 12409448
2018 Geographical distribution of β-globin gene mutations in Syria. Hematology (Amsterdam, Netherlands) 20 29637841
2000 Polymorphism and divergence in the beta-globin replication origin initiation region. Molecular biology and evolution 20 10666717
1988 Cellular factor affecting the stability of beta-globin mRNA. Gene 20 3163661
2023 Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway. Science China. Life sciences 18 38155279
2007 Using 5'-PTMs to repair mutant beta-globin transcripts. RNA (New York, N.Y.) 18 17556711
2010 Evaluation of real-time PCR targeting hbb gene for Borrelia species identification. Journal of microbiological methods 17 20451566
2009 Clinical and hematological characteristics of uncommon beta-globin variants in Thailand. International journal of hematology 17 19440680
2002 Chromatin structure and transcriptional regulation of the beta-globin locus. Experimental cell research 17 12126952
1987 Selective solubilization of beta-globin oligonucleosomes at low ionic strength. Biochemistry 17 3828304
2018 Genetic and Epigenetic Mechanisms of β-Globin Gene Switching. Biochemistry. Biokhimiia 16 29626925
2013 Distinctive mutation spectrum of the HBB gene in an urban eastern Indian population. Hemoglobin 16 24099628
2010 Region-specific genetic heterogeneity of HBB mutation distribution in South-Western Greece. Hemoglobin 16 20642331
2009 Interaction of Borrelia burgdorferi Hbb with the p66 promoter. Nucleic acids research 15 19910373
2004 A high throughput beta-globin genotyping method by multiplexed melting temperature analysis. Molecular genetics and metabolism 15 14972330
2024 Bacterial histone HBb from Bdellovibrio bacteriovorus compacts DNA by bending. Nucleic acids research 14 38864377
2017 Epigenetic interplay at the β-globin locus. Biochimica et biophysica acta. Gene regulatory mechanisms 14 28161275
2015 β-Globin Mutations in Egyptian Patients With β-Thalassemia. Laboratory medicine 14 25617386
2015 Characterization of Deletions of the HBA and HBB Loci by Array Comparative Genomic Hybridization. The Journal of molecular diagnostics : JMD 14 26612711
2006 Polymorphisms in the HBB gene relate to individual cardiorespiratory adaptation in response to endurance training. British journal of sports medicine 14 16990440
2004 The mammalian beta globin origin of DNA replication. Frontiers in bioscience : a journal and virtual library 14 15358579
1977 Maintenance of the ratio of alpha and beta globin synthesis in rabbit reticulocytes. European journal of biochemistry 14 923589
2014 β-globin genes: mutation hot-spots in the global thalassemia belt. Hemoglobin 12 25523871
2006 Thalassaemia-like carriers not linked to the beta-globin gene cluster. British journal of haematology 11 16445840