Affinage

GATA1

Erythroid transcription factor · UniProt P15976

Length
413 aa
Mass
42.8 kDa
Annotated
2026-04-28
100 papers in source corpus 49 papers cited in narrative 49 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GATA1 is a dual zinc finger transcription factor that serves as the master regulator of erythroid, megakaryocytic, and eosinophil lineage commitment and terminal differentiation, while also promoting erythroid precursor survival. Its C-terminal zinc finger binds WGATAR motifs and its N-terminal finger independently recognizes GATC motifs, and GATA1 assembles distinct activating complexes (with CBP/p300, Brd3, P-TEFb, TAL1) and repressive complexes (via FOG-1 recruitment of NuRD/MeCP1, and ETO2) to coordinate gene activation (e.g., globins, EpoR, EKLF, miR-144/451) and repression (e.g., GATA-2) during hematopoiesis (PMID:2776214, PMID:9553047, PMID:15920471, PMID:18625887, PMID:18303114). GATA1 activity is tuned by acetylation (by CBP/p300, required for chromatin occupancy and subsequently triggering ubiquitin-proteasome degradation), SUMOylation (inhibitory, reversed by SENP1), and caspase-3 cleavage (from which Hsp70 protects GATA1 during normal differentiation) (PMID:9859997, PMID:16888089, PMID:16858405, PMID:20457756, PMID:17167422). Germline mutations in GATA1 that disrupt FOG-1 interaction cause X-linked dyserythropoietic anemia and thrombocytopenia, and acquired GATA1 mutations producing the truncated GATA-1s isoform are associated with Down syndrome–related acute megakaryoblastic leukemia (PMID:10700180, PMID:12172547).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1989 High

    Identification of GATA-1 as an erythroid-specific zinc finger transcription factor that binds globin gene regulatory regions established the first lineage-restricted DNA-binding regulator of erythropoiesis.

    Evidence cDNA cloning and DNA-binding assays from erythroid cells

    PMID:2776214

    Open questions at the time
    • No in vivo loss-of-function data yet
    • Function of the two individual zinc fingers not yet resolved
  2. 1993 High

    Demonstrating that the two zinc fingers have distinct DNA-binding specificities (C-finger for GATA, both fingers for TAAG cores) and that GATA-1 activates megakaryocyte-specific promoters expanded the mechanistic model beyond erythroid-only regulation.

    Evidence Random oligonucleotide selection with mutant GATA-1 proteins; megakaryocyte reporter assays with mutagenesis

    PMID:8262042 PMID:8408012

    Open questions at the time
    • In vivo relevance of dual motif binding not tested
    • N-finger-specific target genes not identified
  3. 1994 High

    NMR structure of the GATA-1–DNA complex revealed monomeric binding with predominantly hydrophobic base contacts in the major groove, providing the first atomic-level understanding of GATA factor DNA recognition.

    Evidence Multidimensional heteronuclear NMR spectroscopy of GATA-1 finger–DNA complex

    PMID:8081746

    Open questions at the time
    • Structure of the full-length protein or multi-finger complex not determined
    • No structural data for GATA-1 bound to non-canonical GATC motifs
  4. 1995 High

    Self-association of GATA-1 via its zinc finger domains and its interaction with GATA-2/GATA-3, combined with its essential role in erythroid precursor survival, revealed that GATA-1 functions both as a multimerizing transcriptional activator and an anti-apoptotic factor.

    Evidence GST pulldown with domain mapping and transcriptional superactivation assays; GATA-1-null ES cell differentiation with apoptosis readout

    PMID:7568185 PMID:7739529

    Open questions at the time
    • Survival target genes not identified
    • Oligomeric state on chromatin in vivo unknown
  5. 1996 High

    GATA-1-null embryonic lethality with proerythroblast arrest established GATA-1 as essential for both primitive and definitive erythropoiesis in vivo, solidifying its master-regulator status.

    Evidence Germline gene targeting in mice with embryonic phenotype analysis

    PMID:8901585

    Open questions at the time
    • Contribution to other lineages not yet addressed by this model
  6. 1997 High

    Lineage-selective knockout showed GATA-1 is independently required for megakaryocyte maturation and platelet biogenesis, revealing a dual-lineage master-regulator function.

    Evidence Targeted cis-element deletion ablating megakaryocyte GATA-1 expression in mice

    PMID:9233806

    Open questions at the time
    • Megakaryocyte-specific target gene program not defined
  7. 1998 High

    Discovery that FOG-1 is an essential GATA-1 cofactor—with FOG-1-null mice phenocopying GATA-1 deficiency—and that acetylation by p300/CBP enhances GATA-1 DNA binding established two major regulatory axes controlling GATA-1 function.

    Evidence FOG-1 gene targeting in mice; in vitro acetyltransferase assays with in vivo acetylation confirmation and mutagenesis

    PMID:10207073 PMID:9553047 PMID:9859997

    Open questions at the time
    • How acetylation affects chromatin (vs. naked DNA) binding not yet addressed
    • Structural basis of FOG-1–GATA-1 interaction unknown
  8. 1999 High

    Identification of caspase-mediated GATA-1 cleavage as a mechanism linking death-receptor signaling to erythroid failure, with rescue by a caspase-resistant mutant, revealed a direct post-translational switch controlling erythroid survival.

    Evidence Death receptor stimulation, caspase assays, rescue with caspase-resistant GATA-1 mutant

    PMID:10519553

    Open questions at the time
    • Identity of the protecting factor not yet known (later identified as Hsp70)
  9. 2000 High

    Human GATA1 mutations (V205M, G208S) that disrupt FOG-1 interaction were identified as causal for X-linked dyserythropoietic anemia and thrombocytopenia, providing the first disease-mechanism link for GATA1.

    Evidence Family genetic analysis with in vitro FOG-1 interaction assays and erythroid rescue in G1E cells

    PMID:10700180 PMID:11675338

    Open questions at the time
    • Full spectrum of GATA1 mutations causing disease not yet cataloged
    • In vivo structural basis of FOG-1 binding disruption not resolved
  10. 2002 High

    Discovery of acquired GATA1 mutations in Down syndrome AMKL producing the GATA-1s truncation, and eosinophil-lineage loss from GATA-1 promoter mutation, expanded the disease and lineage repertoire of GATA1 beyond erythroid and megakaryocytic defects.

    Evidence Sequencing of DS-AMKL patient samples with biochemical characterization of GATA-1s; targeted GATA-binding site deletion in mice

    PMID:12045237 PMID:12172547

    Open questions at the time
    • Mechanism by which GATA-1s specifically drives megakaryoblast expansion not explained
    • Whether GATA-1s acts as dominant negative or loss-of-function in vivo unclear
  11. 2003 High

    Proteomic identification of GATA-1 complexes with FOG-1/MeCP1 for repression and CBP/TAL-1/Gfi-1b for activation, together with kinetic ChIP showing GATA-1 drives histone acetylation at beta-globin, defined the activating and repressive chromatin-remodeling mechanisms of GATA-1.

    Evidence Biotinylation-tagging proteomics in erythroid cells, kinetic ChIP in conditional GATA-1 G1E cells

    PMID:12556492 PMID:15920471

    Open questions at the time
    • Order of complex assembly on chromatin not fully resolved
    • Stoichiometry of activating vs. repressive complexes unknown
  12. 2005 High

    Demonstration that FOG-1 links GATA-1 to the NuRD corepressor complex and that FOG-1 facilitates the GATA switch (GATA-2→GATA-1 replacement at chromatin) established the mechanism by which GATA-1 displaces GATA-2 during differentiation.

    Evidence FOG-1 mutagenesis abolishing NuRD binding; ChIP in FOG-1-null cells for GATA factor switching

    PMID:14715908 PMID:15920470 PMID:16286657

    Open questions at the time
    • Whether NuRD enzymatic activity is required for the switch not tested
    • Kinetics of GATA switch at genome-wide scale not characterized
  13. 2006 High

    Hsp70 was identified as the nuclear protector of GATA-1 from caspase-3 cleavage, with erythropoietin withdrawal causing Hsp70 nuclear export and consequent GATA-1 destruction, thereby coupling growth-factor signaling to transcription-factor stability.

    Evidence Co-IP, confocal imaging, in vitro caspase protection assay, siRNA knockdown with caspase-resistant GATA-1 rescue

    PMID:17167422

    Open questions at the time
    • Mechanism of Hsp70 nuclear-cytoplasmic shuttling not resolved
    • Whether other chaperones participate unknown
  14. 2006 High

    Acetylation was shown to be essential for GATA-1 chromatin occupancy in vivo (not just naked-DNA binding) and to subsequently trigger GATA-1 ubiquitin-proteasomal degradation cooperatively with MAPK phosphorylation, revealing an activation-coupled degradation cycle.

    Evidence ChIP with acetylation-defective GATA-1 mutant; proteasome/ubiquitin pathway inhibitor studies with phosphorylation analysis

    PMID:16858405 PMID:16888089

    Open questions at the time
    • E3 ubiquitin ligase responsible not identified
    • Whether this cycle operates at all target genes or is promoter-selective
  15. 2008 High

    GATA-1 was found to regulate erythropoiesis through direct activation of the miR-144/451 locus and to control megakaryocyte maturation by recruiting P-TEFb and by forming repressive complexes with ETO2, broadening its functional toolkit beyond conventional transcriptional activation.

    Evidence ChIP and morpholino knockdown in zebrafish (miR); co-IP, shRNA knockdown, and pharmacologic Cdk9 inhibition (P-TEFb); biotinylated pulldown/proteomics and ChIP (ETO2)

    PMID:18303114 PMID:18625887 PMID:18780834

    Open questions at the time
    • Full spectrum of GATA-1-regulated miRNAs not cataloged
    • Mechanism of ETO2 dissociation during terminal differentiation unknown
  16. 2010 High

    SUMOylation was established as an inhibitory modification of GATA-1, with SENP1-mediated deSUMOylation required for GATA-1 chromatin occupancy and definitive erythropoiesis, adding a third post-translational switch to the GATA-1 regulatory logic.

    Evidence SENP1-knockout mice, in vitro deSUMOylation assays, ChIP, PIASy gain-of-function

    PMID:20457756

    Open questions at the time
    • SUMOylation sites on GATA-1 not mapped at residue level
    • Interplay between SUMOylation and acetylation not resolved
  17. 2011 High

    Brd3 was identified as a reader of acetylated GATA-1 via its first bromodomain, with GATA-1 being the major determinant of Brd3 genomic recruitment, explaining how acetylation couples GATA-1 to BET-dependent transcriptional elongation.

    Evidence Co-IP, ChIP-seq in GATA-1-null vs. replete cells, BD1 mutagenesis, BET inhibitor treatment

    PMID:21536911

    Open questions at the time
    • Whether Brd4 has overlapping function not resolved
    • Structural basis of Brd3-acetyl-GATA-1 interaction not determined
  18. 2014 High

    Selective translational sensitivity of GATA1 mRNA to ribosomal protein haploinsufficiency linked Diamond-Blackfan anemia pathogenesis to reduced GATA-1 protein levels, revealing that GATA-1 abundance is a critical bottleneck in erythropoiesis.

    Evidence Translational profiling, GATA-1 target signature analysis in DBA patient cells, GATA-1 overexpression rescue

    PMID:24952648

    Open questions at the time
    • Specific features of GATA1 mRNA that confer translational sensitivity not identified
    • Whether other lineage-critical mRNAs are co-regulated unknown
  19. 2015 High

    ChIP-exo revealed that GATA-1 and TAL1 co-occupy ~4,000 sites in a precisely organized compound motif (TG + WGATAA spaced 7–8 bp), defining the genome-wide architectural grammar of the core erythroid transcription-factor complex.

    Evidence ChIP-exo with 5′ exonuclease digestion and deep sequencing, motif analysis

    PMID:26503782

    Open questions at the time
    • Whether motif spacing determines activating vs. repressive outcome unknown
    • Three-dimensional chromatin contacts at these sites not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • The E3 ubiquitin ligase that targets acetylated GATA-1 for proteasomal degradation, the structural basis of the full GATA-1/FOG-1/NuRD ternary complex, and the mechanism by which GATA-1 mRNA is selectively sensitive to ribosomal haploinsufficiency remain unresolved.
  • E3 ligase identity unknown
  • Full ternary complex structure not determined
  • cis-regulatory features of GATA1 mRNA conferring translational sensitivity undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1266738 Developmental Biology 4 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1643685 Disease 2
Partners
BRD3CBFA2T3CBPEP300GFI1BSPI1TAL1ZFPM1
Complex memberships
GATA-1/FOG-1/NuRDGATA-1/P-TEFbGATA-1/TAL1 pentameric complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 GATA-1 (Eryf1) is a zinc finger transcription factor that binds DNA sites within regulatory regions of alpha- and beta-globin gene families in erythroid cells; its cDNA encodes a basic 38 kDa protein with a pair of Cys-x-x-Cys-x17-Cys-x-x-Cys zinc fingers required for sequence-specific DNA binding. cDNA cloning, DNA binding assays, erythroid-specific expression analysis Cell High 2776214
1991 GATA-1 activates the erythropoietin receptor (EpoR) promoter and is necessary and sufficient as the sole cell-restricted regulator for its activation in fibroblast transfection assays. Promoter transfection assays in fibroblasts with forced GATA-1 expression Proceedings of the National Academy of Sciences of the United States of America High 1660143
1991 GATA-1 acts as a positive regulator of its own promoter through an upstream double GATA motif, establishing a positive feedback loop; in vivo footprinting confirmed protein binding to proximal CACCC box and the upstream GATA motif in erythroid cells. Promoter characterization, in vivo footprinting, transfection assays Genes & development High 2044960
1993 A testis-specific GATA-1 mRNA is transcribed from a distinct promoter located 5' upstream of the erythroid first exon; the GATA-1 protein expressed in erythroid cells is identical to that in Sertoli cells of seminiferous tubules. Northern blot, RT-PCR, monoclonal antibody immunostaining, promoter mapping Nature High 8464479
1993 The two zinc finger domains of GATA-1 have different DNA binding specificities: the C-terminal finger binds GAT(A/T) motifs alone, while binding of both fingers is required for (T/C)AAG core motifs. Random oligonucleotide selection, mutant GATA-1 binding assays, depurination analysis The EMBO journal High 8262042
1993 GATA-1 regulates the platelet glycoprotein IIb (GPIIb) gene promoter in megakaryocytic cells by binding to GATA motifs; the -463 GATA site in an enhancer region is essential for full transcriptional activity. Gel shift assay, supershift with anti-GATA-1 antibody, point mutagenesis, CAT reporter transfection The Journal of biological chemistry High 8408012
1994 GATA-1 is phosphorylated on 6 serines in its amino terminus in uninduced MEL cells, and a 7th site (serine 310) becomes phosphorylated upon DMSO-induced differentiation; phosphorylation does not significantly alter DNA-binding affinity, specificity, or transcriptional transactivation. Phosphorylation mapping by overexpression in COS cells, mutagenesis, DNA binding and transcription assays The Journal of biological chemistry High 8206977
1994 GATA-1 directly activates the EKLF (erythroid Krüppel-like factor) gene promoter through a GATA motif at -60; GATA-1 can activate the EKLF promoter in nonerythroid cells by forced expression, placing EKLF downstream of GATA-1 in erythroid regulatory hierarchy. Promoter analysis, cotransfection with forced GATA-1 expression, mutagenesis of binding sites The Journal of biological chemistry High 8195185
1994 GATA-1 and DNA complex structure determined by NMR: GATA-1 binds as a monomer to the asymmetric consensus (T/A)GATA(A/G); specific contacts with DNA bases in the major groove are predominantly hydrophobic, with water molecules located at the protein-phosphate backbone interface but excluded from the protein-base interface. Multidimensional heteronuclear NMR, water-selective 2D NMR spectroscopy Structure High 8081746
1995 GATA-1 self-associates via its zinc finger region; the minimal domain for self-association maps to 40 amino acids within the C-terminal zinc finger; self-association can recruit a DNA-binding-defective GATA-1 to DNA-bound GATA-1, resulting in transcriptional superactivation. GATA-1 also physically interacts with GATA-2 and GATA-3 via the zinc finger domain. GST pulldown with bacterially expressed proteins, whole-cell extract co-association, transcription assays, deletion mutagenesis Molecular and cellular biology High 7739529
1995 GATA-1 is required for erythroid precursor survival; GATA-1-deficient erythroid cells die by apoptosis despite normal expression of known GATA target genes and independent of p53 accumulation, demonstrating a cell survival function distinct from its role in erythroid gene activation. GATA-1-null ES cell in vitro differentiation, apoptosis assays Proceedings of the National Academy of Sciences of the United States of America High 7568185
1995 Ligand-activated estrogen receptor (ER) represses GATA-1 transcriptional activity in a ligand-dependent, reversible manner; GATA-1 and ER physically interact via the GATA-1 finger region and N-terminal activation domain, as shown by in vitro binding and co-immunoprecipitation from transfected COS cells. Co-immunoprecipitation from transfected COS cells, in vitro binding, transcriptional reporter assays Molecular and cellular biology High 7760810
1996 GATA-1 is essential for erythroid differentiation in vivo; male GATA-1-null mouse embryos die between E10.5-E11.5 with erythroid cells arrested at an early proerythroblast stage, establishing an essential role in both embryonic and definitive erythropoiesis. Gene targeting in ES cells, germline transmission, embryo phenotype analysis Proceedings of the National Academy of Sciences of the United States of America High 8901585
1997 GATA-1 is critical for megakaryocyte growth regulation and platelet biogenesis; lineage-selective loss of megakaryocyte GATA-1 expression results in markedly reduced platelet numbers, deregulated megakaryocyte proliferation, and severely impaired cytoplasmic maturation. Targeted mutation of cis-elements upstream of GATA-1 locus to achieve lineage-selective knockout in mice The EMBO journal High 9233806
1997 GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis: a 5' element (-3.9 to -2.6 kb) drives primitive erythroid expression, while a first intron element is required for definitive erythroid expression and cooperates with the upstream element. Transgenic mouse reporter assays with 5' and intron deletion constructs Proceedings of the National Academy of Sciences of the United States of America High 9114016
1998 GATA-1 N-finger self-association involves reciprocal N-finger–C-finger contacts rather than N-finger homodimerization; a 25-residue region C-terminal to the core N-finger is sufficient for interaction with intact GATA-1, and mutations disrupting self-association also impair transcriptional activation. In vitro binding with purified domains, deletion/mutation analysis, transfection-based transcription assays The Journal of biological chemistry High 9804826
1998 FOG-1 (Friend of GATA-1) is an essential cofactor for GATA-1 in erythropoiesis and megakaryopoiesis; FOG-1-null mice die with severe anemia showing partial erythroid maturation block similar to GATA-1 deficiency, and megakaryocytes fail to develop. Gene targeting in mice, embryo analysis, lineage-specific cell development analysis Genes & development High 9553047
1998 GATA-1 is acetylated in vitro by p300, which significantly increases GATA-1 DNA binding and alters mobility of GATA-1-DNA complexes; GATA-1 is also acetylated in vivo, and mutagenesis of acetylated residues reveals a relationship between acetylation and GATA-1 in vivo function and GATA-1-dependent transcription. In vitro acetyltransferase assay with p300, EMSA, in vivo [3H]acetate labeling, mutagenesis Nature High 9859997
1999 CBP acetylates GATA-1 at two conserved lysine-rich motifs at the C-terminal tails of both zinc fingers; GATA-1 is acetylated in vivo at these same CBP-acetylated sites; mutations in acetylation motifs partially or completely abrogate GATA-1-dependent erythroid differentiation without affecting DNA binding. [3H]acetate labeling, anti-acetyl-lysine immunoprecipitation, mutagenesis, erythroid differentiation rescue assay in G1E cells Molecular and cellular biology High 10207073
1999 Caspase-mediated cleavage of GATA-1 occurs in immature erythroid cells exposed to death-receptor ligands or upon erythropoietin starvation, leading to impaired erythroid development; a caspase-resistant GATA-1 mutant fully restores erythroid expansion and differentiation following death receptor triggering. Death receptor stimulation assays, caspase cleavage assays, rescue with caspase-resistant GATA-1 mutant Nature High 10519553
2000 A V205M missense mutation in the N-terminal zinc finger of GATA-1, identified in a family with X-linked dyserythropoietic anemia and thrombocytopenia, abrogates interaction between GATA-1 and its cofactor FOG-1, inhibiting erythroid differentiation rescue in GATA-1-deficient erythroid cells. Family genetic analysis, in vitro interaction assays, erythroid cell rescue assay in G1E cells Nature genetics High 10700180
2001 The N-terminal zinc finger of GATA-1 binds GATC motifs in DNA (distinct from the C-finger's GATA motif preference); cellular assays confirm GATA-1 can activate promoters containing GATC sites via its N-finger. The disease-associated mutation R216Q abolishes N-finger DNA binding. In vitro DNA binding assays, mutant GATA-1 cell-based reporter assays The Journal of biological chemistry High 11445591
2001 G208S mutation in the GATA-1 N-terminal zinc finger domain, found in a family with X-linked thrombocytopenia, partially disrupts GATA-1-FOG interaction, particularly with FOG zinc finger 9, establishing that the GATA-1-FOG interaction is required for normal in vivo megakaryocyte and erythroid development. Genetic linkage, sequencing, in vitro interaction assays Blood High 11675338
2001 In vivo domain analysis of GATA-1 in transgenic mice shows: the C-terminal zinc finger (CF) is essential for both primitive and definitive erythropoiesis; the N-terminal activation domain (NT) is dispensable for primitive but required for definitive erythropoiesis; the N-terminal zinc finger (NF) is dispensable for primitive erythropoiesis but required for definitive hematopoiesis. Transgenic rescue of GATA-1 germline mutant mice with domain deletion constructs The EMBO journal High 11566888
2002 Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in mice, demonstrating that GATA-1 is required for eosinophil specification through positive autoregulation of its own expression. Targeted promoter mutation in mice, lineage analysis The Journal of experimental medicine High 12045237
2002 Acquired mutations in GATA1 in Down syndrome acute megakaryoblastic leukemia (DS-AMKL) introduce premature stop codons preventing full-length GATA-1 synthesis but allowing production of a shorter isoform (GATA-1s) lacking the N-terminal activation domain; GATA-1s binds DNA and interacts with FOG-1 comparably to full-length but has reduced transactivation potential. Sequencing of DS-AMKL samples, in vitro binding assays, transactivation assays Nature genetics High 12172547
2002 FOG-1 has distinct domains that differentially influence erythroid versus megakaryocytic maturation; interaction through only one of FOG-1's four GATA-binding zinc fingers is sufficient for rescue of either lineage, arguing against a model of FOG-1 bridging multiple GATA-binding DNA elements. FOG-1 domain deletion/mutagenesis, rescue assay in FOG-1-null cell line Molecular and cellular biology High 12024038
2003 GATA-1 directly activates EKLF expression and represses GATA-2; GATA-1 forms distinct activating and repressive complexes in erythroid cells interacting with Gfi-1b, the repressive MeCP1 complex, and the ACF/WCRF chromatin remodeling complex in addition to FOG-1 and TAL-1; FOG-1 mediates GATA-1 interactions with the MeCP1 complex. Biotinylation tagging/proteomics in erythroid cells, co-immunoprecipitation, ChIP The EMBO journal High 15920471
2003 GATA-1 forms a histone acetylation pattern at the beta-globin locus; restoration of GATA-1 in G1E cells rapidly increases acetylation of histones H3 and H4 at the beta-globin promoter and LCR, correlating with GATA-1 and CBP occupancy at the locus in vivo. ChIP in GATA-1-deficient G1E cells with conditional GATA-1, time-course experiments Molecular and cellular biology High 12556492
2004 FOG-1 facilitates chromatin occupancy by GATA-1 at sites previously bound by GATA-2 (GATA switch); genetic analysis in FOG-1-null hematopoietic precursors showed FOG-1 is critical for GATA switches but not for establishing the active GATA-2 chromatin domain. Genetic complementation in FOG-1-null cells, ChIP for GATA factor binding at multiple loci Proceedings of the National Academy of Sciences of the United States of America High 14715908
2005 FOG-1 binds to the NuRD corepressor complex in vitro and in vivo; a conserved N-terminal domain of FOG-1 is necessary and sufficient for NuRD binding; FOG-1 mutations that abrogate NuRD binding block gene repression by FOG-1; NuRD is present at GATA-1/FOG-1-repressed genes in erythroid cells, establishing that FOG-1 links GATA-1 to histone deacetylation. Co-immunoprecipitation in vitro and in vivo, point mutagenesis of FOG-1, ChIP, reporter repression assays The EMBO journal High 15920470
2005 GATA-1 occupies only a small subset of conserved GATA motifs within the beta-globin locus; GATA-1 preferentially occupies LCR GATA motifs first (in a GATA-1-independent chromatin context), then increases promoter accessibility; GATA-1 recruitment of EKLF and SWI/SNF at restricted LCR sites defines a multistep activation mechanism. Kinetic ChIP in GATA-1-null cells with inducible ER-GATA-1, chromatin accessibility assays Proceedings of the National Academy of Sciences of the United States of America High 16286657
2006 Hsp70 protects GATA-1 from caspase-3-mediated cleavage during terminal erythroid differentiation; Hsp70 co-localizes and interacts with GATA-1 in the nucleus during differentiation; erythropoietin starvation causes nuclear export of Hsp70, allowing GATA-1 cleavage; Hsp70 protects GATA-1 through its peptide-binding domain in vitro; siRNA knockdown of Hsp70 leads to GATA-1 cleavage and apoptosis rescued by caspase-resistant GATA-1. Co-localization imaging, co-immunoprecipitation, in vitro caspase protection assay, siRNA knockdown, caspase-resistant GATA-1 rescue Nature High 17167422
2006 Acetylation of GATA-1 is required for its chromatin occupancy in vivo; acetylation-defective GATA-1 retains nuclear localization, normal steady-state levels, and in vitro DNA binding, but is dramatically impaired in binding all examined cellular target sites by ChIP. ChIP in erythroid cells expressing acetylation-defective GATA-1 mutant Blood High 16888089
2006 Acetylated GATA-1 is targeted for degradation via the ubiquitin/proteasome pathway; acetylation positively signals ubiquitination; MAPK phosphorylation cooperates with acetylation to execute GATA-1 protein degradation in a promoter-specific manner. Ubiquitin pathway inhibitors, proteasome inhibitors, phosphorylation analysis, promoter-specific protein loss assays The EMBO journal High 16858405
2003 GATA-1 and PU.1 physically associate through their DNA-binding domains and mutually inhibit each other's DNA-binding activities; c-Myb also binds GATA-1 and inhibits its DNA-binding; these reciprocal inhibitory interactions are critical for Ras-mediated megakaryocytic lineage fate decisions. Co-immunoprecipitation, in vitro binding, DNA-binding inhibition assays, forced expression in cell lines Blood High 11001896
2004 GATA-1 directly interacts with p53 via the GATA-1 C-terminal zinc finger domain binding the p53 transactivation domain; GATA-1 inhibits p53-dependent transcription in erythroid cells, and this inhibition is reciprocal (p53 can inhibit GATA-1-responsive promoters). In vitro interaction assay, co-immunoprecipitation from erythroid cells, transcription reporter assays, mutagenesis Blood High 19411634
2004 c-Myb and GATA-1 each inhibit each other's transcriptional activity via competition for binding to the co-activator CBP; GATA-1 and c-Myb can each form bipartite complexes with CBP but the tripartite complex is not efficiently formed. Co-immunoprecipitation, transcriptional reporter assays, competitive binding experiments Oncogene Medium 10644988
2004 c-Jun blocks erythroid differentiation by repressing GATA-1 activity; HERP2, a hairy-enhancer-of-split-related factor, is a downstream target of c-Jun that physically interacts with GATA-1 and represses its transcriptional activation, linking Notch signaling to GATA-1 regulation. Forced expression, co-immunoprecipitation, transcription reporter assays, primary human hematopoietic progenitor transduction Molecular and cellular biology Medium 15314183
2008 GATA-1 directly binds a distal upstream regulatory element to activate RNA Pol II-mediated transcription of a single precursor RNA encoding both miR-144 and miR-451; these miRNAs are required for erythroid maturation, revealing a new regulatory axis through which GATA-1 controls erythropoiesis. ChIP, gene complementation strategy, antisense morpholino knockdown in zebrafish, microarray Proceedings of the National Academy of Sciences of the United States of America High 18303114
2008 GATA-1 physically interacts with components of P-TEFb (cyclin T1 and Cdk9); megakaryocytic induction is associated with recruitment of GATA-1 into P-TEFb and dissociation of the Cdk9 inhibitor HEXIM1; Cdk9 activity contributes to megakaryocytic differentiation downstream of GATA-1. Co-immunoprecipitation, shRNA knockdown, pharmacologic Cdk9 inhibition, mouse megakaryocytic GATA-1 deficiency model Blood High 18780834
2008 GATA-1 interacts with the corepressor ETO2 in megakaryocytes; knockdown of ETO2 promotes megakaryocyte differentiation and enhances expression of terminal megakaryocyte genes (e.g., Pf4); ETO2-dependent repression of Pf4 proximal promoter is mediated by GATA-binding sites and an E-box, with direct in vivo binding of ETO2, GATA-1, and SCL pentameric complex to the promoter. In vivo biotinylated GATA-1 pulldown/proteomics, ChIP, shRNA knockdown, reporter assays Blood High 18625887
2010 GATA-1 is SUMOylated in vivo; SUMOylation reduces GATA-1 DNA-binding and its recruitment to GATA1-responsive gene promoters; SENP1 directly deSUMOylates GATA-1 to promote GATA-1-dependent gene expression and definitive erythropoiesis; PIASy promotes GATA-1 SUMOylation and represses its activity. SENP1 knockout mice, bone marrow transplantation, in vitro deSUMOylation assay, ChIP, PIASy cotransfection The Journal of experimental medicine High 20457756
2011 Brd3 binds acetylated GATA-1 via its first bromodomain (BD1) in an acetylation-dependent manner in vitro and in vivo; a single residue mutation in BD1 abolishes acetyl-lysine binding and prevents Brd3 recruitment by GATA-1; GATA-1 is a major determinant of Brd3 genomic recruitment; pharmacologic BET inhibition disrupts the Brd3-GATA-1 interaction and inhibits erythroid maturation. Co-immunoprecipitation, ChIP-seq in GATA-1-null and GATA-1-replete cells, mutagenesis, bromodomain inhibitor treatment Proceedings of the National Academy of Sciences of the United States of America High 21536911
2003 HDAC5 directly associates with GATA-1 and suppresses its transcriptional activity; during MEL cell differentiation, a portion of HDAC5 translocates from nucleus to cytoplasm concomitant with erythroid differentiation, suggesting regulated HDAC5 subcellular distribution contributes to GATA-1 transactivation during differentiation. Co-immunoprecipitation, transcriptional reporter assays, subcellular fractionation/immunofluorescence in MEL cells Oncogene Medium 14668799
2007 TR2 and TR4 orphan nuclear receptors directly repress GATA1 transcription through binding to an evolutionarily conserved direct repeat (DR) element in the GATA-1 hematopoietic enhancer (G1HE); mutation of this DR element elevates Gata1 promoter activity and reduces responsiveness to TR2/TR4. TR2/TR4 transgenic mice, loss-of-function null mice, DR element mutagenesis, ChIP, reporter assays Genes & development High 17974920
2008 Ikaros interacts with GATA-1 and enhances GATA-1 binding to regulatory regions across the beta-globin locus; their combinatorial effect impairs proximity between the locus control region and gamma-globin genes, contributing to gamma-globin gene silencing. ChIP, co-immunoprecipitation, transgenic human beta-globin locus analysis Molecular and cellular biology Medium 19114560
2014 Ribosomal protein haploinsufficiency (the cause of most Diamond-Blackfan anemia cases) leads to decreased GATA-1 mRNA translation, with GATA-1 mRNA having a higher threshold for translation initiation; in DBA patients with RPS19 mutations, GATA-1 target gene signature is globally reduced indicating decreased GATA-1 activity; increasing GATA-1 protein levels partially overcomes DBA hematopoietic defects. Translational analysis, transcriptional profiling of GATA-1 targets in patient cells, GATA-1 protein overexpression rescue Nature medicine High 24952648
2015 ChIP-exo reveals that GATA-1 and TAL1 form a precisely organized complex at a compound genomic motif consisting of a TG dinucleotide 7-8 bp upstream of a WGATAA motif across ~4,000 genomic locations; both factors generate distinct characteristic peak patterns reflecting their positional arrangement within the complex. ChIP-exo (high-resolution ChIP with 5' exonuclease digestion and sequencing), ChIP-seq, 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
1998 Regulation of activity of the transcription factor GATA-1 by acetylation. Nature 610 9859997
1996 Arrested development of embryonic red cell precursors in mouse embryos lacking transcription factor GATA-1. Proceedings of the National Academy of Sciences of the United States of America 603 8901585
2002 Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nature genetics 576 12172547
1989 The erythroid-specific transcription factor Eryf1: a new finger protein. Cell 566 2776214
1997 A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development. The EMBO journal 541 9233806
2002 Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. The Journal of experimental medicine 502 12045237
2000 Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nature genetics 403 10700180
1999 Negative regulation of erythropoiesis by caspase-mediated cleavage of GATA-1. Nature 324 10519553
1991 Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes & development 304 2044960
1995 Development of hematopoietic cells lacking transcription factor GATA-1. Development (Cambridge, England) 291 7867497
1998 Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. Genes & development 285 9553047
2008 A GATA-1-regulated microRNA locus essential for erythropoiesis. Proceedings of the National Academy of Sciences of the United States of America 271 18303114
1995 Transcription factor GATA-1 permits survival and maturation of erythroid precursors by preventing apoptosis. Proceedings of the National Academy of Sciences of the United States of America 268 7568185
1993 Erythroid transcription factor GATA-1 is abundantly transcribed in mouse testis. Nature 268 8464479
2014 Altered translation of GATA1 in Diamond-Blackfan anemia. Nature medicine 243 24952648
2005 GATA-1 forms distinct activating and repressive complexes in erythroid cells. The EMBO journal 237 15920471
2006 Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1. Nature 232 17167422
1992 Rescue of erythroid development in gene targeted GATA-1- mouse embryonic stem cells. Nature genetics 230 1302015
2005 FOG-1 recruits the NuRD repressor complex to mediate transcriptional repression by GATA-1. The EMBO journal 225 15920470
1999 CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at functionally important sites. Molecular and cellular biology 219 10207073
1991 Activation of the erythropoietin receptor promoter by transcription factor GATA-1. Proceedings of the National Academy of Sciences of the United States of America 207 1660143
2011 Bromodomain protein Brd3 associates with acetylated GATA1 to promote its chromatin occupancy at erythroid target genes. Proceedings of the National Academy of Sciences of the United States of America 196 21536911
2005 Loss of gata1 but not gata2 converts erythropoiesis to myelopoiesis in zebrafish embryos. Developmental cell 190 15621534
2003 Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis. Blood 173 12560215
2003 Natural history of GATA1 mutations in Down syndrome. Blood 173 14656875
1995 Self-association of the erythroid transcription factor GATA-1 mediated by its zinc finger domains. Molecular and cellular biology 164 7739529
2006 An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis. Nature genetics 160 16783379
2004 GATA1 in normal and malignant hematopoiesis. Seminars in cell & developmental biology 156 15659348
2003 Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome. Blood 154 12816863
2003 GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages. Immunity 149 14499119
2001 X-linked thrombocytopenia caused by a novel mutation of GATA-1. Blood 145 11675338
1997 GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis. Proceedings of the National Academy of Sciences of the United States of America 142 9114016
2004 Coregulator-dependent facilitation of chromatin occupancy by GATA-1. Proceedings of the National Academy of Sciences of the United States of America 129 14715908
2002 A nonsense mutation in zebrafish gata1 causes the bloodless phenotype in vlad tepes. Proceedings of the National Academy of Sciences of the United States of America 126 11960002
2005 Chromatin domain activation via GATA-1 utilization of a small subset of dispersed GATA motifs within a broad chromosomal region. Proceedings of the National Academy of Sciences of the United States of America 118 16286657
2003 Formation of a tissue-specific histone acetylation pattern by the hematopoietic transcription factor GATA-1. Molecular and cellular biology 114 12556492
1995 Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor. Molecular and cellular biology 113 7760810
1993 The two zinc finger-like domains of GATA-1 have different DNA binding specificities. The EMBO journal 112 8262042
2001 In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis. The EMBO journal 111 11566888
1994 Regulation of the erythroid Kruppel-like factor (EKLF) gene promoter by the erythroid transcription factor GATA-1. The Journal of biological chemistry 103 8195185
2019 Regulation of GATA1 levels in erythropoiesis. IUBMB life 101 31769197
2005 Early block to erythromegakaryocytic development conferred by loss of transcription factor GATA-1. Blood 101 16144799
2013 GATA-1 regulates the generation and function of basophils. Proceedings of the National Academy of Sciences of the United States of America 96 24167252
1994 Phosphorylation of the erythroid transcription factor GATA-1. The Journal of biological chemistry 96 8206977
2003 Identification and characterization of 2 types of erythroid progenitors that express GATA-1 at distinct levels. Blood 95 12893747
1993 A tobacco cDNA clone encoding a GATA-1 zinc finger protein homologous to regulators of nitrogen metabolism in fungi. Molecular & general genetics : MGG 94 8413186
2009 GATA-2 reinforces megakaryocyte development in the absence of GATA-1. Molecular and cellular biology 90 19620289
2008 GATA1-related leukaemias. Nature reviews. Cancer 87 18354416
2007 STAT1 promotes megakaryopoiesis downstream of GATA-1 in mice. The Journal of clinical investigation 85 18060035
2006 Acetylation and MAPK phosphorylation cooperate to regulate the degradation of active GATA-1. The EMBO journal 82 16858405
2002 Distinct domains of the GATA-1 cofactor FOG-1 differentially influence erythroid versus megakaryocytic maturation. Molecular and cellular biology 82 12024038
2003 Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation. Oncogene 80 14668799
2001 The N-terminal zinc finger of the erythroid transcription factor GATA-1 binds GATC motifs in DNA. The Journal of biological chemistry 74 11445591
2006 Acetylation of GATA-1 is required for chromatin occupancy. Blood 73 16888089
2010 SENP1-mediated GATA1 deSUMOylation is critical for definitive erythropoiesis. The Journal of experimental medicine 72 20457756
2008 Human phenotypes associated with GATA-1 mutations. Gene 72 18930124
2001 Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells. The Journal of experimental medicine 72 11714753
2013 GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation. Genes to cells : devoted to molecular & cellular mechanisms 71 23911012
2017 Downregulation of GATA1 drives impaired hematopoiesis in primary myelofibrosis. The Journal of clinical investigation 68 28240607
2004 Leukemogenesis caused by incapacitated GATA-1 function. Molecular and cellular biology 68 15572684
2005 Abnormalities of GATA-1 in megakaryocytes from patients with idiopathic myelofibrosis. The American journal of pathology 67 16127162
1993 The transcription factor GATA-1 regulates the promoter activity of the platelet glycoprotein IIb gene. The Journal of biological chemistry 66 8408012
2014 Loss of GATA-1 full length as a cause of Diamond-Blackfan anemia phenotype. Pediatric blood & cancer 64 24453067
2004 Jun blockade of erythropoiesis: role for repression of GATA-1 by HERP2. Molecular and cellular biology 60 15314183
2011 Defective nuclear localization of Hsp70 is associated with dyserythropoiesis and GATA-1 cleavage in myelodysplastic syndromes. Blood 59 22160620
1998 Transcription factor GATA-1 in megakaryocyte development. Stem cells (Dayton, Ohio) 59 11012179
2008 Ikaros and GATA-1 combinatorial effect is required for silencing of human gamma-globin genes. Molecular and cellular biology 58 19114560
2006 Characterization of GATA-1(+) hemangioblastic cells in the mouse embryo. The EMBO journal 57 17159898
1998 Involvement of the N-finger in the self-association of GATA-1. The Journal of biological chemistry 56 9804826
1991 Transcriptional role of a conserved GATA-1 site in the human epsilon-globin gene promoter. Molecular and cellular biology 56 2017165
2004 Modification of the erythroid transcription factor GATA-1 by SUMO-1. Proceedings of the National Academy of Sciences of the United States of America 55 15173587
2004 GATA-1: friends, brothers, and coworkers. Annals of the New York Academy of Sciences 55 15659837
1992 Delta-thalassemia caused by disruption of the site for an erythroid-specific transcription factor, GATA-1, in the delta-globin gene promoter. Blood 55 1515647
2008 Characterization of megakaryocyte GATA1-interacting proteins: the corepressor ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation. Blood 51 18625887
2007 Gata1 regulates dendritic-cell development and survival. Blood 51 17505015
2013 Ikaros inhibits megakaryopoiesis through functional interaction with GATA-1 and NOTCH signaling. Blood 49 23335373
1997 The level of the tissue-specific factor GATA-1 affects the cell-cycle machinery. Genes and function 49 9680325
2009 GATA-1 associates with and inhibits p53. Blood 48 19411634
2005 GATA-1: one protein, many partners. The international journal of biochemistry & cell biology 48 16095949
2000 Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines. Blood 48 11001896
1998 Testicular GATA-1 factor up-regulates the promoter activity of rat inhibin alpha-subunit gene in MA-10 Leydig tumor cells. Molecular endocrinology (Baltimore, Md.) 48 9514155
2000 Inhibitory interaction of c-Myb and GATA-1 via transcriptional co-activator CBP. Oncogene 47 10644988
2008 Cross-talk of GATA-1 and P-TEFb in megakaryocyte differentiation. Blood 46 18780834
2007 The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription. Genes & development 45 17974920
2020 Smad2/3-pathway ligand trap luspatercept enhances erythroid differentiation in murine β-thalassaemia by increasing GATA-1 availability. Journal of cellular and molecular medicine 44 32351032
1997 Upstream and downstream of erythroid transcription factor GATA-1. Genes to cells : devoted to molecular & cellular mechanisms 44 9167968
1989 Increased erythroid-specific expression of a mutated HPFH gamma-globin promoter requires the erythroid factor NFE-1. Nucleic acids research 44 2474800
1993 Downregulation of GATA-1 expression during phorbol myristate acetate-induced megakaryocytic differentiation of human erythroleukemia cells. Blood 43 8443382
2010 The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism. Oncogene 42 20101202
2015 Genome-Wide Organization of GATA1 and TAL1 Determined at High Resolution. Molecular and cellular biology 39 26503782
2000 Inositol polyphosphate 4-phosphatase type I regulates cell growth downstream of transcription factor GATA-1. Proceedings of the National Academy of Sciences of the United States of America 39 11087841
2008 The role of transcriptional activator GATA-1 at human beta-globin HS2. Nucleic acids research 38 18586828
2005 Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells. Blood 38 16174764
1994 Localization of bound water in the solution structure of a complex of the erythroid transcription factor GATA-1 with DNA. Structure (London, England : 1993) 38 8081746
1995 Homotypic interactions of chicken GATA-1 can mediate transcriptional activation. Molecular and cellular biology 37 7862128
2019 GATA1 mutations in red cell disorders. IUBMB life 34 31652397
2003 Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1. Cancer research 33 14559825
2011 Inherited thrombocytopenia due to GATA-1 mutations. Seminars in thrombosis and hemostasis 32 22102271
1993 Characterization of the mouse gene that encodes the delta/YY1/NF-E1/UCRBP transcription factor. Proceedings of the National Academy of Sciences of the United States of America 32 8516301
2000 GATA-1 is a potential repressor of anti-Müllerian hormone expression during the establishment of puberty in the mouse. Molecular reproduction and development 31 10813843