Affinage

GATA1

Erythroid transcription factor · UniProt P15976

Length
413 aa
Mass
42.8 kDa
Annotated
2026-06-10
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GATA-1 is a dual zinc-finger, erythroid-restricted transcription factor that orchestrates erythroid, megakaryocytic, and eosinophilic differentiation by binding WGATAR DNA elements and acting as both activator and repressor (PMID:2776214, PMID:8262042, PMID:7758949). Its C-terminal zinc finger is the primary DNA-binding domain and is essential for both primitive and definitive erythropoiesis, while the N-terminal finger contributes to definitive erythropoiesis and confers nuclear localization (PMID:8262042, PMID:7862128, PMID:11566888). GATA-1 is required for erythropoiesis—its loss blocks globin expression and drives committed precursors into p53-independent apoptosis—and it enforces lineage survival and maturation by directly activating EpoR and bcl-xL and by autoregulating its own locus (PMID:1302015, PMID:7568185, PMID:10381501, PMID:1660143, PMID:2014222). It couples differentiation to cell-cycle exit by directly occupying and repressing c-Myc and c-Kit, the latter silencing the downstream Vav1/Rac1/Akt axis to enforce G1 arrest as a program genetically separable from maturation (PMID:12832487, PMID:16024808). GATA-1 executes opposing transcriptional outputs through context-specific complexes: activating assemblies with TAL-1, FOG-1, and CBP/p300, and repressive assemblies in which FOG-1 recruits the NuRD corepressor (and, at select loci, GFI1B and PRC2/EZH2) (PMID:15920471, PMID:15920470, PMID:22778136, PMID:26503782); genome-wide, GATA1 and TAL1 co-bind a precisely organized compound E-box/GATA motif (PMID:26503782). Its activity is gated by post-translational modification—CBP/p300-mediated acetylation of the zinc-finger tails is required for chromatin occupancy in vivo (distinct from intrinsic DNA binding), and erythropoietin-driven PI3K/AKT phosphorylation of Ser310 enhances transcriptional output—while late-stage HSP27-facilitated ubiquitin-proteasomal degradation removes GATA-1 to permit terminal maturation (PMID:10207073, PMID:16888089, PMID:16204311, PMID:20410505). GATA-1 also reciprocally antagonizes the myeloid factor PU.1, whose N-terminus blocks GATA-1 DNA binding and which tethers pRB to repress GATA-1 targets, defining the erythroid-versus-myeloid fate switch (PMID:10364157, PMID:10753833, PMID:11023493, PMID:14559995). Reduced GATA-1 protein from impaired mRNA translation underlies the hematopoietic defect of RPS19-mutant Diamond-Blackfan anemia (PMID:24952648).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1989 High

    Established the molecular identity of the erythroid DNA-binding activity, defining GATA-1 as a zinc-finger transcription factor recognizing WGATAR elements in globin regulatory regions.

    Evidence cDNA cloning and DNA-binding assays reconstituting erythroid binding activity

    PMID:2776214

    Open questions at the time
    • Did not define in vivo developmental requirement
    • Cofactors and complex composition unknown
  2. 1991 Medium

    Showed GATA-1 directly controls target promoters governing erythroid survival and its own expression, introducing autoregulation and EpoR control.

    Evidence Fibroblast and erythroid promoter-reporter transfection, DNase footprinting of the GATA-1 and EpoR promoters

    PMID:1660143 PMID:2014222

    Open questions at the time
    • Gain-of-function in non-erythroid cells, single lab
    • In vivo relevance of autoregulation not yet tested
  3. 1992 High

    Demonstrated that GATA-1 is genetically required for erythropoiesis and sufficient to instruct megakaryocytic fate, establishing it as a master lineage-determining factor.

    Evidence ES-cell knockout with transgene rescue; enforced expression in a myeloid line

    PMID:1302015 PMID:1385117

    Open questions at the time
    • Mechanism of lineage instruction unresolved
    • Survival vs transcriptional roles not separated
  4. 1993 High

    Dissected functional division of labor between the two zinc fingers, identifying the C-finger as the primary DNA-binding domain with distinct motif specificities.

    Evidence Oligonucleotide selection, EMSA with finger mutants, depurination analysis

    PMID:8262042

    Open questions at the time
    • In vivo lineage-specific finger requirements not yet addressed
    • N-finger function beyond binding unclear
  5. 1995 High

    Separated GATA-1's anti-apoptotic survival function from its transcriptional gene-regulatory role and revealed dosage-dependent lineage reprogramming.

    Evidence GATA-1-null ES differentiation with apoptosis assays; graded retroviral expression in transformed myeloblasts

    PMID:7568185 PMID:7758949

    Open questions at the time
    • Survival effector gene not yet identified
    • Dosage-sensing mechanism unknown
  6. 1996 Medium

    Identified differentiation-coupled nuclear translocation of GATA-1 as a regulatory step, linking nuclear entry to repression of c-myb/GATA-2 and induction of differentiation genes.

    Evidence Immunofluorescence and a GATA-1/estrogen-receptor conditional system in avian progenitors

    PMID:9012505

    Open questions at the time
    • Trigger for translocation undefined
    • Avian system; mammalian generality unconfirmed
  7. 1998 High

    Identified CBP/p300 as a GATA-1 coactivator required for erythroid differentiation, linking GATA-1 to chromatin-modifying machinery.

    Evidence Reciprocal Co-IP from erythroid extracts, domain mapping, conditional E1A interference in MEL cells

    PMID:9482838

    Open questions at the time
    • Whether CBP acts via acetylation of GATA-1 not yet shown
    • Target loci not mapped
  8. 1999 High

    Defined PU.1 as a direct GATA-1 antagonist and bcl-xL as a survival effector, establishing both the lineage-switch logic and the anti-apoptotic output.

    Evidence Co-IP and reporter assays with PU.1 domain mutants in MEL/Xenopus; parallel bcl-xL/GATA-1 knockout epistasis

    PMID:10364157 PMID:10381501

    Open questions at the time
    • Molecular basis of PU.1 inhibition not yet pinpointed
    • Direct GATA-1 occupancy of bcl-xL not demonstrated
  9. 1999 High

    Showed CBP acetylates GATA-1 zinc-finger tails and that these modifications are required for differentiation despite no effect on in vitro DNA binding, predicting a chromatin-level function for acetylation.

    Evidence Metabolic acetate labeling, anti-acetyl-lysine IP, acetylation-site mutagenesis with rescue assay

    PMID:10207073

    Open questions at the time
    • Mechanistic basis of acetylation-dependent function unresolved at the time
    • Other modifications not integrated
  10. 2000 High

    Mapped the bidirectional GATA-1/PU.1 antagonism to specific domains: PU.1's N-terminus blocks GATA-1 DNA binding, and GATA-1's C-finger represses PU.1 independently of its own DNA binding.

    Evidence EMSA with purified proteins, pulldowns, domain mutants, and cell-line reprogramming assays

    PMID:10753833 PMID:11023493

    Open questions at the time
    • Genomic loci of mutual repression not mapped
    • Stoichiometry in vivo unknown
  11. 2001 High

    Established lineage- and stage-specific domain requirements in vivo, showing the C-finger is essential throughout while the N-finger and transactivation domain have restricted roles.

    Evidence Transgenic mouse rescue of GATA-1 mutants with domain-deletion constructs

    PMID:11566888

    Open questions at the time
    • Molecular partners distinguishing primitive vs definitive contexts unspecified
  12. 2003 High

    Connected GATA-1 to cell-cycle exit by demonstrating direct repression of c-Myc, genetically separating proliferation arrest from erythroid maturation.

    Evidence Inducible GATA-1 rescue, microarray, ChIP at the Myc promoter, Myc-overexpression epistasis

    PMID:12832487

    Open questions at the time
    • Corepressor machinery at Myc not defined here
    • Upstream signals coupling to arrest unclear
  13. 2003 Medium

    Expanded the partner repertoire to RUNX1/CBFbeta cooperation and to PU.1-mediated tethering of pRB at repressed GATA-1 targets, refining repression mechanisms.

    Evidence Co-IP, reporter assays, ChIP and domain mutagenesis; HDAC3/4/5 interaction studies

    PMID:12576332 PMID:14559995 PMID:14668799

    Open questions at the time
    • Generality across loci varies by study
    • HDAC and pRB contributions not integrated genome-wide
  14. 2003 High

    Defined FOG-1 as the determinant of context-dependent GATA-1 chromatin occupancy and chromatin modification, varying by locus.

    Evidence ChIP with a FOG-1-binding-defective GATA-1(V205M) mutant across multiple loci

    PMID:14695898

    Open questions at the time
    • Why FOG-1 dependence differs by locus unexplained
    • Downstream effector complexes not yet identified
  15. 2005 High

    Resolved the activating vs repressive complex identities and the EpoR-AKT signaling input, providing the combinatorial logic for GATA-1's dual transcriptional outputs.

    Evidence Proteomics/Co-IP defining TAL-1/FOG-1 activating and Gfi-1b/NuRD/ACF repressive complexes; FOG-1-NuRD interaction mapping; AKT in vitro kinase assay on Ser310

    PMID:15920470 PMID:15920471 PMID:16204311

    Open questions at the time
    • Switch governing activating vs repressive complex assembly undefined
    • How Ser310 phosphorylation alters complex choice unknown
  16. 2005 High

    Showed GATA-1 represses c-Kit and its downstream Vav1/Rac1/Akt axis to drive arrest, reinforcing separation of cell-cycle from maturation programs.

    Evidence ChIP at the Kit element and epistasis by sustaining individual signaling components in G1E cells

    PMID:16024808

    Open questions at the time
    • Corepressors at the Kit locus not specified
  17. 2006 High

    Demonstrated that acetylation is required for in vivo chromatin occupancy, mechanistically explaining the earlier acetylation-dependent differentiation defect.

    Evidence ChIP with an acetylation-defective mutant across loci, contrasting unaltered in vitro DNA binding

    PMID:16888089

    Open questions at the time
    • Molecular reader of acetylated GATA-1 not identified
    • Relationship to CBP recruitment unresolved
  18. 2007 Medium

    Linked GATA-1 to transcriptional elongation and to autoregulatory repression by TR2/TR4, broadening its mechanistic and regulatory context.

    Evidence P-TEFb Co-IP/inhibition in megakaryocytes; ChIP/EMSA/reporter at the G1HE direct-repeat with TR2/TR4 gain/loss-of-function

    PMID:17974920 PMID:18780834

    Open questions at the time
    • P-TEFb recruitment generality across loci unknown
    • Single lab for elongation findings
  19. 2008 High

    Identified a non-coding effector arm by showing GATA-1 directly activates the miR-144/451 locus required for erythroid maturation.

    Evidence ChIP at the miRNA enhancer and morpholino depletion in zebrafish

    PMID:18303114

    Open questions at the time
    • miRNA target genes mediating the phenotype not enumerated
  20. 2009 Medium

    Revealed that NuRD mediates both activation and repression of GATA-1/FOG-1 targets in vivo and identified GATA-1/p53 cross-antagonism.

    Evidence Mouse knock-in disrupting FOG-1/NuRD plus ChIP/expression profiling; in vitro and Co-IP GATA-1/p53 interaction with reporter assays

    PMID:19411634 PMID:19927129

    Open questions at the time
    • How NuRD switches between activating and repressing outputs unclear
    • p53 interaction single lab, in vivo significance untested
  21. 2010 Medium

    Defined the terminal-maturation off-switch: HSP27-facilitated, modification-dependent ubiquitin-proteasomal degradation of GATA-1.

    Evidence HSP27 siRNA, Co-IP, and ubiquitination assays in erythroid differentiation models

    PMID:20410505

    Open questions at the time
    • E3 ligase identity not established
    • Single lab
  22. 2015 High

    Provided high-resolution architecture of the GATA1-TAL1 co-binding complex at a defined compound motif genome-wide.

    Evidence ChIP-exo with exonuclease footprinting and ChIP-seq validation, computational motif analysis

    PMID:26503782

    Open questions at the time
    • Functional consequence of precise spacing per locus not dissected
  23. 2014 High

    Connected GATA-1 dosage to human disease by showing impaired GATA-1 mRNA translation under ribosomal haploinsufficiency drives the Diamond-Blackfan anemia phenotype.

    Evidence Polysome profiling and transcriptional signature analysis of DBA patient cells with GATA-1 protein rescue

    PMID:24952648

    Open questions at the time
    • Why GATA-1 mRNA is selectively translation-sensitive not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • What molecular switch directs assembly of activating (TAL-1/FOG-1/CBP) versus repressive (FOG-1/NuRD/GFI1B/PRC2) GATA-1 complexes at a given locus remains the central open question.
  • Integration of acetylation, Ser310 phosphorylation, sumoylation, and FOG-1 occupancy into a single decision model lacking
  • Reader proteins for modified GATA-1 unidentified
  • Functional significance of sumoylation unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 1
Partners
CREBBP (CBP)FOG1 (ZFPM1)GFI1BRB1 (PRB)RUNX1SPI1 (PU.1)TAL1TP53
Complex memberships
GATA-1/FOG-1/NuRD repressive complexGATA-1/TAL-1/FOG-1 activating complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 GATA-1 (Eryf1/NFE-1) was identified as an erythroid-specific transcription factor containing a pair of Cys-x-x-Cys-x17-Cys-x-x-Cys zinc finger motifs that confer sequence-specific DNA binding to WGATAR motifs in regulatory regions of alpha- and beta-globin genes; the cloned cDNA encodes the specific DNA-binding activity found in erythrocytes. cDNA cloning, DNA-binding assays, biochemical characterization Cell High 2776214
1989 The erythroid-specific factor NFE-1 (GATA-1) binds to the -175 region of the gamma-globin promoter; mutations that increase NFE-1 binding at this site cause hereditary persistence of fetal hemoglobin, demonstrating that GATA-1 binding is required for the increased promoter activity. Transfection reporter assays, site-directed mutagenesis of GATA motif Nucleic acids research Medium 2474800
1991 GATA-1 is necessary and sufficient as the sole cell-restricted regulator to activate the erythropoietin receptor (EpoR) promoter, establishing that GATA-1 directly controls the EpoR gene to ensure survival of erythroid progenitors. Fibroblast transfection assays with GATA-1 expression plasmid and EpoR promoter-reporter constructs Proceedings of the National Academy of Sciences of the United States of America Medium 1660143
1991 The GATA-1 gene promoter contains clustered GATA-1 binding sites protected by erythroid nuclear extracts and purified GATA-1, and the upstream region functions as a powerful promoter in erythroid cells; cotransfection of GATA-1 cDNA increases promoter activity in fibroblasts, indicating GATA-1 plays an autoregulatory role in its own expression. DNase I footprinting, gel mobility shift assay, transfection reporter assays Proceedings of the National Academy of Sciences of the United States of America Medium 2014222
1992 GATA-1 is required for both primitive (yolk sac) and definitive (fetal liver) erythropoiesis; targeted disruption blocks development completely at the level of globin RNA expression, and rescue depends on a putative autoregulatory GATA motif in the distal promoter. Gene targeting in embryonic stem cells, in vitro differentiation, transgene rescue assay Nature genetics High 1302015
1992 Enforced GATA-1 expression in an early myeloid cell line (416B) induces megakaryocytic differentiation, demonstrating that GATA-1 can act as a lineage-determining factor for the megakaryocytic lineage. Retroviral expression of GATA-1 in myeloid cell line, morphological and biochemical differentiation markers The EMBO journal Medium 1385117
1993 The two zinc finger-like domains of GATA-1 have different DNA-binding specificities: the carboxy finger alone binds GAT(A/T) motifs associated with transcriptional activation, while both fingers together are required to bind (T/C)AAG motifs; the C-finger is the primary DNA-binding domain. Random oligonucleotide selection, EMSA with wild-type and mutant GATA-1 proteins, depurination analysis The EMBO journal High 8262042
1993 GATA-1 is expressed from a distinct testis-specific promoter in murine Sertoli cells using common downstream exons; the same protein found in erythroid cells is expressed in the seminiferous tubules, where it is restricted to the basement membrane region. Northern blotting, immunohistochemistry with anti-GATA-1 monoclonal antibody, RNase protection Nature Medium 8464479
1994 GATA-1 is phosphorylated on 6 serines within its amino terminus in uninduced MEL cells, and a 7th site (serine 310) becomes phosphorylated upon DMSO-induced differentiation; however, phosphorylation at these sites does not significantly affect DNA-binding affinity, specificity, DNA bending, or transcriptional transactivation. Metabolic labeling, phosphopeptide mapping, mutagenesis, COS cell overexpression, transcriptional assays The Journal of biological chemistry High 8206977
1994 GATA-1 is expressed specifically in Sertoli cells in the mouse testis; expression is induced with the first wave of spermatogenesis and is negatively regulated by maturing germ cells, as shown by uniform expression in germ-cell-deficient mutant mice. Immunostaining, Northern blotting, analysis of mutant mice (W/Wv, jsd/jsd, cryptorchid) Development (Cambridge, England) Medium 7924983
1995 Loss of GATA-1 causes committed erythroid precursors to undergo apoptosis; this cell death occurs despite normal expression of GATA target genes including EpoR and is p53-independent, demonstrating GATA-1 has a survival function distinct from its transcriptional role in erythroid gene regulation. In vitro differentiation of GATA-1-null ES cells, apoptosis assays, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 7568185
1995 Forced GATA-1 expression in Myb-Ets-transformed myeloblasts reprograms them into eosinophils, thromboblasts, or erythroblasts depending on expression level, demonstrating that GATA-1 acts as a lineage-determining transcription factor and that its dosage influences cell fate choice. Retroviral overexpression of GATA-1 in avian hematopoietic cell lines, lineage marker analysis Genes & development Medium 7758949
1995 GATA-1 N-terminal zinc finger (finger I) contains an independent nuclear localization function; homotypic GATA-1 protein-protein interactions occur in solution demonstrated by co-immunoprecipitation, and these interactions can mediate transcriptional activation in vivo. One-hybrid system, co-immunoprecipitation, transient transfection transcription assays Molecular and cellular biology Medium 7862128
1996 In avian erythroid progenitors, GATA-1 protein is predominantly cytoplasmic; differentiation-induced nuclear translocation of GATA-1 constitutes a critical regulatory step, and nuclear GATA-1 simultaneously suppresses c-myb and GATA-2 transcription while inducing differentiation genes. Immunofluorescence subcellular localization, GATA-1/estrogen receptor fusion protein system, gene expression analysis Development (Cambridge, England) Medium 9012505
1998 CBP/p300 markedly stimulates GATA-1 transcriptional activity; GATA-1 and CBP co-immunoprecipitate from erythroid nuclear extracts; interaction maps to the zinc finger region of GATA-1 and the E1A-binding region of CBP; E1A expression blocks erythroid differentiation and GATA-1 target gene expression in an E1A/CBP-interaction-dependent manner. Co-immunoprecipitation, domain mapping, transient transfection, conditional E1A expression in MEL cells Proceedings of the National Academy of Sciences of the United States of America High 9482838
1999 CBP acetylates GATA-1 at conserved lysine-rich motifs at the C-terminal tails of both zinc fingers; GATA-1 is acetylated in vivo at these same sites; mutations in either acetylation motif partially impair GATA-1-induced erythroid differentiation, and mutations in both completely abrogate it, while acetylation does not alter GATA-1 DNA-binding activity in vitro. [3H]acetate labeling, anti-acetyl-lysine immunoprecipitation, site-directed mutagenesis, GATA-1-null cell line differentiation rescue assay Molecular and cellular biology High 10207073
1999 PU.1 directly interacts with GATA-1, requiring intact DNA-binding domains in both proteins; PU.1 represses GATA-1-mediated transcriptional activation; both the DNA-binding and transactivation domains of PU.1 are required for repression; ectopic GATA-1 relieves PU.1-imposed block to erythroid differentiation in MEL cells and Xenopus embryos. Co-immunoprecipitation, co-transfection reporter assays, domain-deletion mutagenesis, Xenopus erythropoiesis assay Genes & development High 10364157
1999 GATA-1 and erythropoietin cooperate to induce bcl-xL expression in erythroid cells; GATA-1 strongly and selectively induces bcl-xL (not bcl-2 or mcl-1), and bcl-xL-null ES cells phenocopy the GATA-1 null erythroid maturation defect, placing bcl-xL as a critical downstream effector of GATA-1-mediated survival. In vitro ES cell differentiation, bcl-xL-null and GATA-1-null genetic analysis, mRNA/protein expression analysis Blood High 10381501
2000 GATA-1 directly interacts with the PU.1 ETS domain through its C-terminal zinc finger; GATA-1 represses PU.1-dependent myeloid transcription independently of its own DNA binding, and this repression requires the PU.1 DNA-binding domain as the target rather than the PU.1 transactivation domain. In vitro pulldown assays, co-transfection reporter assays, domain-deletion mutagenesis, myeloid cell line reprogramming Blood High 10753833
2000 PU.1 N-terminal 70 amino acids specifically block GATA-1 DNA binding; PU.1 interacts with the C-terminal zinc finger of GATA-1 through both N- and C-termini; but only the N-terminus (not C-terminus) is required for inhibiting GATA-1 function; demonstrated with purified proteins in EMSA. EMSA with purified proteins, K562 inducible overexpression, G1ER cell differentiation assay Blood High 11023493
2001 In vivo domain-deletion analysis shows that the C-terminal zinc finger (CF) is essential for both primitive and definitive erythropoiesis; the N-terminal zinc finger (NF) is required for definitive but not primitive erythropoiesis; the N-terminal transactivation domain is dispensable for definitive hematopoiesis, revealing lineage-specific domain requirements. Transgenic mouse rescue of GATA-1 germline mutants with domain-deletion constructs The EMBO journal High 11566888
2003 GATA-1 promotes G1 cell cycle arrest during erythroid maturation by repressing c-Myc expression; GATA-1 occupies the Myc promoter in vivo by ChIP; GATA-1 also represses CDK6 and cyclin D2 and induces p18INK4C and p27Kip1; enforced Myc prevents GATA-1-induced cell cycle arrest but not erythroid maturation, demonstrating these are genetically separable programs. Synchronous inducible GATA-1 rescue assay, microarray, chromatin immunoprecipitation, Myc overexpression epistasis Molecular and cellular biology High 12832487
2003 RUNX1 physically interacts with GATA-1 and cooperates functionally with GATA-1 and CBFbeta to activate a megakaryocytic promoter; the RUNX1-ETO leukemic fusion protein potently represses GATA-1-mediated transactivation. Co-immunoprecipitation, co-transfection reporter assays, immunostaining of primary bone marrow Blood Medium 12576332
2003 PU.1 binds GATA-1 on DNA and tethers pRB (retinoblastoma protein) to GATA-1 target genes; pRB is required for PU.1-mediated repression of GATA-1; PU.1 repression maps to a small acidic N-terminal domain that binds the C pocket of pRB; PU.1, pRB, and GATA-1 colocalize at repressed GATA-1 target genes. ChIP, co-immunoprecipitation, domain mutagenesis, differentiation assays Molecular and cellular biology High 14559995
2003 Context-dependent regulation by FOG-1: FOG-1 interaction is required for GATA-1 chromatin occupancy at select sites (beta-globin promoter, HS2) and for histone acetylation there, but is dispensable for GATA-1 binding and histone acetylation at other sites (HS3, EKLF gene); at the GATA-2 gene, FOG-1 is required for GATA-1-induced histone deacetylation and transcriptional repression but not DNA occupancy. Chromatin immunoprecipitation, GATA-1(V205M) FOG-1-binding-defective mutant, inducible GATA-1-ER system Proceedings of the National Academy of Sciences of the United States of America High 14695898
2004 GATA-1 is modified by SUMO-1 at a single lysine residue in vivo and in vitro; the nuclear RING finger protein PIASy promotes GATA-1 sumoylation and dramatically represses its transcriptional activity; a non-sumoylatable mutant is functionally indistinguishable from wild-type GATA-1 in reporter and Xenopus assays, leaving the functional significance of sumoylation uncertain. In vitro sumoylation assay, co-transfection with PIASy, site-directed mutagenesis, Xenopus explant assay Proceedings of the National Academy of Sciences of the United States of America Medium 15173587
2005 GATA-1 forms distinct protein complexes in erythroid cells: activating complexes with TAL-1 and FOG-1, and repressive complexes including Gfi-1b, the MeCP1/Mi-2/NuRD complex, and the ACF/WCRF chromatin remodeling complex; FOG-1 mediates GATA-1 interaction with the MeCP1 complex. Biotinylation tagging/proteomics in erythroid cells, co-immunoprecipitation, ChIP at target gene subsets The EMBO journal High 15920471
2005 FOG-1 recruits the NuRD corepressor complex to mediate GATA-1-dependent transcriptional repression; the interaction is mediated by a conserved N-terminal domain of FOG-1; point mutations in FOG-1 that abrogate NuRD binding block gene repression; NuRD is present at GATA-1/FOG-1-repressed genes in erythroid cells in vivo. In vitro binding assays, co-immunoprecipitation in vivo, ChIP, point mutagenesis, erythroid differentiation assay The EMBO journal High 15920470
2005 Erythropoietin stimulates phosphorylation of GATA-1 at serine 310 via the PI3-kinase/AKT signaling pathway; AKT phosphorylates GATA-1-S310 in vitro and in erythroid cells and enhances GATA-1 transcriptional activity; this phosphorylation is important for Epo-induced erythroid maturation. In vitro kinase assay with AKT, phospho-specific antibody, PI3K inhibition, fetal liver erythroid progenitor differentiation assay Blood High 16204311
2005 GATA-1 represses c-Kit expression by directly occupying a Kit gene regulatory element (shown by ChIP), and thereby represses the downstream Vav1/Rac1/Akt signaling axis to promote cell cycle arrest; sustained expression of individual signaling components (c-Kit, Vav1, Rac1, Akt) inhibits GATA-1-induced cell cycle arrest without affecting erythroid maturation markers. ChIP, inducible GATA-1 G1E system, overexpression of signaling components, flow cytometric cell cycle analysis Molecular and cellular biology High 16024808
2006 Acetylation of GATA-1 is required for chromatin occupancy in vivo; an acetylation-defective GATA-1 mutant retains normal nuclear localization, protein stability, and in vitro DNA binding, but is dramatically impaired in binding to all examined target sites in chromatin as shown by ChIP. Chromatin immunoprecipitation, site-directed mutagenesis of acetylation sites, erythroid differentiation assay Blood High 16888089
2007 GATA-1 physically and functionally interacts with components of positive transcription elongation factor P-TEFb (cyclin T1 and Cdk9); megakaryocytic induction recruits GATA-1 to P-TEFb while dissociating the Cdk9 inhibitor HEXIM1; pharmacologic Cdk9 inhibition impairs megakaryocytic differentiation. Co-immunoprecipitation, shRNA knockdown, pharmacologic inhibition, mouse megakaryocyte differentiation assays Blood Medium 18780834
2007 GATA-1 directly binds the GATA-1 locus hematopoietic enhancer (G1HE) through an evolutionarily conserved direct repeat element; TR2 and TR4 orphan nuclear receptors bind this same DR element in vitro and in vivo to repress GATA-1 transcription in erythroid progenitors; mutation of the DR element elevates promoter activity and reduces TR2/TR4 responsiveness. ChIP, EMSA, promoter reporter assays, TR2/TR4 overexpression and shRNA knockdown in murine and human erythroid cells Genes & development High 17974920
2008 GATA-1 directly binds a distal upstream regulatory element to activate RNA Pol II-mediated transcription of a common precursor RNA encoding miR-144 and miR-451; miR-451 depletion impairs erythroid maturation, defining a new GATA-1 regulatory axis. ChIP demonstrating GATA-1 occupancy of miRNA locus, morpholino knockdown in zebrafish, gene complementation Proceedings of the National Academy of Sciences of the United States of America High 18303114
2009 GATA-1 directly interacts with p53 in vitro (C-terminal zinc finger domain of GATA-1 binds the p53 transactivation domain) and in erythroid cells by co-immunoprecipitation; GATA-1 overexpression inhibits p53-responsive promoter activation, and p53 reciprocally inhibits GATA-1-responsive promoter activation. In vitro interaction assay, co-immunoprecipitation from erythroid cells, co-transfection reporter assays, mutagenesis Blood Medium 19411634
2009 NuRD is present at both repressed and active GATA-1/FOG-1 target genes; disruption of the FOG-1/NuRD interaction in mice causes anemia and macrothrombocytopenia and impairs both transcriptional activation and repression of select GATA-1/FOG-1 targets, demonstrating that NuRD mediates both activating and repressive functions of GATA-1. Mouse knock-in disrupting FOG-1/NuRD interaction, ChIP, gene expression analysis in primary erythroid cells and megakaryocytes The EMBO journal High 19927129
2010 HSP27 acts as a chaperone/E3-ligase facilitator for GATA-1; in late erythroid differentiation, p38-phosphorylated HSP27 enters the nucleus, binds acetylated GATA-1, and promotes its ubiquitination and proteasomal degradation, thereby downregulating GATA-1 protein levels to enable terminal maturation. siRNA depletion of HSP27 in erythroid differentiation models, co-immunoprecipitation, ubiquitination assays, pharmacologic inhibition Blood Medium 20410505
2003 GATA-1 directly interacts with HDAC3, HDAC4, and HDAC5; coexpression of HDAC5 suppresses GATA-1 transcriptional activity; during MEL cell differentiation, a portion of HDAC5 relocalizes from nucleus to cytoplasm, correlating with relief of GATA-1 repression. Co-immunoprecipitation, co-transfection reporter assays, confocal immunofluorescence of HDAC5 subcellular localization during differentiation Oncogene Medium 14668799
2012 GATA-1 recruits FOG-1 and subsequently NuRD (MI-2/ATPase), GFI1B, and the Polycomb repressive complex 2 (PRC2/EZH2) to the Hes1 locus; EZH2-mediated H3K27 methylation is required for Hes1 repression; Ikaros facilitates GATA-1 recruitment to the locus. ChIP demonstrating co-recruitment at Hes1 locus, RNAi depletion of EZH2, Ikaros-deficient primary cell analysis Molecular and cellular biology Medium 22778136
2014 Ribosomal protein haploinsufficiency (RPS19 mutations causing Diamond-Blackfan anemia) reduces GATA-1 mRNA translation, possibly due to a higher translation-initiation threshold for GATA-1 mRNA; this globally and specifically reduces GATA-1 target gene expression amplitude without affecting GATA-1 mRNA levels; increasing GATA-1 protein levels partially rescues DBA hematopoietic defects. Polysome profiling, transcriptional signature analysis of primary DBA patient cells, GATA-1 protein rescue experiments Nature medicine High 24952648
2015 High-resolution ChIP-exo shows that GATA1 and TAL1 form a precisely organized complex at a compound motif (TG dinucleotide located 7-8 bp upstream of WGATAA) across ~4,000 genomic locations; the juxtaposition of partial E-box and GATA motif is the predominant co-binding configuration genome-wide. ChIP-exo with 5'-to-3' exonuclease mapping, ChIP-seq validation, computational motif analysis Molecular and cellular biology High 26503782

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 The erythroid-specific transcription factor Eryf1: a new finger protein. Cell 567 2776214
1999 Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. Genes & development 386 10364157
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