Home LiteratureArticle Details
PMID: 12857954 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

GATA-1-dependent transcriptional repression of GATA-2 via disruption of positive autoregulation and domain-wide chromatin remodeling.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 15 ·2003-07-22 ·Pages 8811-6

Grass JA, Boyer ME, Pal S, Wu J, Weiss MJ, Bresnick EH

Abstract

Interplay among GATA transcription factors is an important determinant of cell fate during hematopoiesis. Although GATA-2 regulates hematopoietic stem cell function, mechanisms controlling GATA-2 expression are undefined. Of particular interest is the repression of GATA-2, because sustained GATA-2 expression in hematopoietic stem and progenitor cells alters hematopoiesis. GATA-2 transcription is derepressed in erythroid precursors lacking GATA-1, but the underlying mechanisms are unknown. Using chromatin immunoprecipitation analysis, we show that GATA-1 binds a highly restricted upstream region of the approximately 70-kb GATA-2 domain, despite >80 GATA sites throughout the domain. GATA-2 also binds this region in the absence of GATA-1. Genetic complementation studies in GATA-1-null cells showed that GATA-1 rapidly displaces GATA-2, which is coupled to transcriptional repression. GATA-1 also displaces CREB-binding protein (CBP), despite the fact that GATA-1 binds CBP in other contexts. Repression correlates with reduced histone acetylation domain-wide, but not altered methylation of histone H3 at lysine 4. The GATA factor-binding region exhibited cell-type-specific enhancer activity in transient transfection assays. We propose that GATA-1 instigates GATA-2 repression by means of disruption of positive autoregulation, followed by establishment of a domain-wide repressive chromatin structure. Such a mechanism is predicted to be critical for the control of hematopoiesis.

MeSH Terms
Animals Base Sequence Binding Sites/genetics Cell Line Chromatin/chemistry,metabolism DNA/genetics DNA-Binding Proteins/chemistry,genetics,metabolism Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor GATA2 Transcription Factor Hematopoiesis Histones/chemistry,metabolism Homeostasis Humans Mice Models, Biological Molecular Sequence Data Protein Structure, Tertiary Repressor Proteins/chemistry,genetics,metabolism Transcription Factors/chemistry,genetics,metabolism Transcription, Genetic
Chemicals
Chromatin DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor GATA1 protein, human GATA2 Transcription Factor GATA2 protein, human Gata1 protein, mouse Gata2 protein, mouse Histones Repressor Proteins Transcription Factors DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Grass Jeffrey A
Molecular and Cellular Pharmacology Program, Department of Pharmacology, University of Wisconsin Medical School, 383 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA.
Boyer Meghan E
Pal Saumen
Wu Jing
Weiss Mitchell J
Bresnick Emery H
References (75)
75 references, click to expand
  1. Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: the GATA-1:FOG complex.
    Mol Cell. 1999 Feb;3(2):219-28 PMID: 10078204
  2. CREB-Binding protein acetylates hematopoietic transcription factor GATA-1 at functionally important sites.
    Mol Cell Biol. 1999 May;19(5):3496-505 PMID: 10207073
  3. Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers.
    EMBO J. 1999 May 17;18(10):2812-22 PMID: 10329627
  4. Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene.
    Development. 1999 Jun;126(12):2799-811 PMID: 10331989
  5. Expression and genetic interaction of transcription factors GATA-2 and GATA-3 during development of the mouse central nervous system.
    Dev Biol. 1999 Jun 15;210(2):305-21 PMID: 10357893
  6. The mouse GATA-2 gene is expressed in the para-aortic splanchnopleura and aorta-gonads and mesonephros region.
    Blood. 1999 Jun 15;93(12):4196-207 PMID: 10361117
  7. Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types.
    Cell. 1999 May 28;97(5):587-98 PMID: 10367888
  8. GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression.
    Blood. 1999 Jul 1;94(1):87-96 PMID: 10381501
  9. Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1.
    Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8705-10 PMID: 10411939
  10. A GATA-2/estrogen receptor chimera functions as a ligand-dependent negative regulator of self-renewal.
    Genes Dev. 1999 Jul 15;13(14):1847-60 PMID: 10421636
  11. FOG acts as a repressor of red blood cell development in Xenopus.
    Development. 2000 May;127(10):2031-40 PMID: 10769228
  12. PipMaker--a web server for aligning two genomic DNA sequences.
    Genome Res. 2000 Apr;10(4):577-86 PMID: 10779500
  13. Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human beta-globin locus.
    Genes Dev. 2000 Apr 15;14(8):940-50 PMID: 10783166
  14. Regulation of B lymphocyte and macrophage development by graded expression of PU.1.
    Science. 2000 May 26;288(5470):1439-41 PMID: 10827957
  15. GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies.
    Blood. 2000 Aug 1;96(3):910-6 PMID: 10910904
  16. GATA2 is required for the generation of V2 interneurons.
    Development. 2000 Sep;127(17):3829-38 PMID: 10934027
  17. The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression.
    J Biol Chem. 2000 Dec 15;275(50):38949-52 PMID: 11042222
  18. Patterns of histone acetylation suggest dual pathways for gene activation by a bifunctional locus control region.
    EMBO J. 2000 Dec 15;19(24):6814-22 PMID: 11118216
  19. Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14494-9 PMID: 11121052
  20. Hematopoietic regulatory domain of gata1 gene is positively regulated by GATA1 protein in zebrafish embryos.
    Development. 2001 Jun;128(12):2341-50 PMID: 11493553
  21. Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus.
    Science. 2001 Sep 28;293(5539):2453-5 PMID: 11498546
  22. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries.
    Science. 2001 Aug 10;293(5532):1150-5 PMID: 11498594
  23. Histone acetylation beyond promoters: long-range acetylation patterns in the chromatin world.
    Bioessays. 2001 Sep;23(9):820-30 PMID: 11536294
  24. Distinct mechanisms control RNA polymerase II recruitment to a tissue-specific locus control region and a downstream promoter.
    Mol Cell. 2001 Aug;8(2):465-71 PMID: 11545748
  25. Histone deacetylase 3 associates with and represses the transcription factor GATA-2.
    Blood. 2001 Oct 1;98(7):2116-23 PMID: 11567998
  26. Retinoid signaling regulates primitive (yolk sac) hematopoiesis.
    Blood. 2002 Apr 1;99(7):2379-86 PMID: 11895770
  27. Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo.
    Mol Cell Biol. 2002 May;22(9):3121-8 PMID: 11940669
  28. Cooperative interaction of Xvent-2 and GATA-2 in the activation of the ventral homeobox gene Xvent-1B.
    J Biol Chem. 2002 Jun 28;277(26):23872-81 PMID: 11964398
  29. Distinct domains of the GATA-1 cofactor FOG-1 differentially influence erythroid versus megakaryocytic maturation.
    Mol Cell Biol. 2002 Jun;22(12):4268-79 PMID: 12024038
  30. Transcriptional regulation of erythropoiesis: an affair involving multiple partners.
    Oncogene. 2002 May 13;21(21):3368-76 PMID: 12032775
  31. Essential and instructive roles of GATA factors in eosinophil development.
    J Exp Med. 2002 Jun 3;195(11):1379-86 PMID: 12045236
  32. Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo.
    J Exp Med. 2002 Jun 3;195(11):1387-95 PMID: 12045237
  33. Dissecting long-range transcriptional mechanisms by chromatin immunoprecipitation.
    Methods. 2002 Jan;26(1):27-36 PMID: 12054902
  34. GATA-2 and GATA-2/ER display opposing activities in the development and differentiation of blood progenitors.
    EMBO J. 2002 Jun 17;21(12):3060-9 PMID: 12065419
  35. GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis.
    Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9237-42 PMID: 12077323
  36. The GATA family (vertebrates and invertebrates).
    Curr Opin Genet Dev. 2002 Aug;12(4):416-22 PMID: 12100886
  37. Cooperative activities of hematopoietic regulators recruit RNA polymerase II to a tissue-specific chromatin domain.
    Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11760-5 PMID: 12193659
  38. Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors.
    EMBO J. 2002 Oct 1;21(19):5225-34 PMID: 12356738
  39. Hematopoietic-specific activators establish an overlapping pattern of histone acetylation and methylation within a mammalian chromatin domain.
    Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14309-14 PMID: 12379744
  40. Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates.
    Immunity. 2002 Nov;17(5):665-76 PMID: 12433372
  41. Histone deacetylase-dependent establishment and maintenance of broad low-level histone acetylation within a tissue-specific chromatin domain.
    Biochemistry. 2002 Dec 24;41(51):15152-60 PMID: 12484752
  42. Rescue of erythroid development in gene targeted GATA-1- mouse embryonic stem cells.
    Nat Genet. 1992 May;1(2):92-8 PMID: 1302015
  43. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1.
    Nature. 1991 Jan 17;349(6306):257-60 PMID: 1987478
  44. Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter.
    Genes Dev. 1991 Jun;5(6):919-31 PMID: 2044960
  45. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family.
    Genes Dev. 1990 Oct;4(10):1650-62 PMID: 2249770
  46. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells.
    Nature. 1989 Jun 8;339(6224):446-51 PMID: 2725678
  47. Pluripotent hematopoietic stem cells contain high levels of mRNA for c-kit, GATA-2, p45 NF-E2, and c-myb and low levels or no mRNA for c-fms and the receptors for granulocyte colony-stimulating factor and interleukins 5 and 7.
    Proc Natl Acad Sci U S A. 1995 May 9;92(10):4601-5 PMID: 7538677
  48. GATA transcription factors: key regulators of hematopoiesis.
    Exp Hematol. 1995 Feb;23(2):99-107 PMID: 7828675
  49. Development of hematopoietic cells lacking transcription factor GATA-1.
    Development. 1995 Jan;121(1):163-72 PMID: 7867497
  50. Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells.
    Genes Dev. 1994 May 15;8(10):1184-97 PMID: 7926723
  51. An early haematopoietic defect in mice lacking the transcription factor GATA-2.
    Nature. 1994 Sep 15;371(6494):221-6 PMID: 8078582
  52. DNA-binding specificity of GATA family transcription factors.
    Mol Cell Biol. 1993 Jul;13(7):3999-4010 PMID: 8321207
  53. DNA-binding specificities of the GATA transcription factor family.
    Mol Cell Biol. 1993 Jul;13(7):4011-22 PMID: 8321208
  54. A positive role for histone acetylation in transcription factor access to nucleosomal DNA.
    Cell. 1993 Jan 15;72(1):73-84 PMID: 8422685
  55. Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner.
    Genes Dev. 1993 Jun;7(6):1097-109 PMID: 8504932
  56. A dominant chromatin-opening activity in 5' hypersensitive site 3 of the human beta-globin locus control region.
    EMBO J. 1996 Feb 1;15(3):562-8 PMID: 8599939
  57. A palindromic regulatory site within vertebrate GATA-1 promoters requires both zinc fingers of the GATA-1 DNA-binding domain for high-affinity interaction.
    Mol Cell Biol. 1996 May;16(5):2238-47 PMID: 8628290
  58. Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro.
    EMBO J. 1996 May 15;15(10):2508-18 PMID: 8665858
  59. Temporal mapping of gene expression levels during the differentiation of individual primary hematopoietic cells.
    Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13158-63 PMID: 8917561
  60. Erythroid-cell-specific properties of transcription factor GATA-1 revealed by phenotypic rescue of a gene-targeted cell line.
    Mol Cell Biol. 1997 Mar;17(3):1642-51 PMID: 9032291
  61. The tumor suppressor Smad4/DPC 4 as a central mediator of Smad function.
    Curr Biol. 1997 Apr 1;7(4):270-6 PMID: 9094310
  62. GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4487-92 PMID: 9114016
  63. Arrest in primitive erythroid cell development caused by promoter-specific disruption of the GATA-1 gene.
    J Biol Chem. 1997 May 9;272(19):12611-5 PMID: 9139715
  64. Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation.
    Blood. 1997 May 15;89(10):3636-43 PMID: 9160668
  65. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins.
    EMBO J. 1997 Jun 2;16(11):3145-57 PMID: 9214632
  66. An upstream, DNase I hypersensitive region of the hematopoietic-expressed transcription factor GATA-1 gene confers developmental specificity in transgenic mice.
    Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7976-81 PMID: 9223298
  67. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation.
    Cell. 1997 Jul 11;90(1):109-19 PMID: 9230307
  68. A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development.
    EMBO J. 1997 Jul 1;16(13):3965-73 PMID: 9233806
  69. Alternative promoters regulate transcription of the mouse GATA-2 gene.
    J Biol Chem. 1998 Feb 6;273(6):3625-34 PMID: 9452491
  70. CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation.
    Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2061-6 PMID: 9482838
  71. Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG.
    Genes Dev. 1998 Apr 15;12(8):1176-88 PMID: 9553047
  72. Mechanisms of transcription in eosinophils: GATA-1, but not GATA-2, transactivates the promoter of the eosinophil granule major basic protein gene.
    Blood. 1998 May 1;91(9):3447-58 PMID: 9558404
  73. Disruption of higher-order folding by core histone acetylation dramatically enhances transcription of nucleosomal arrays by RNA polymerase III.
    Mol Cell Biol. 1998 Aug;18(8):4629-38 PMID: 9671473
  74. Alternate promoters and developmental modulation of expression of the chicken GATA-2 gene in hematopoietic progenitor cells.
    J Biol Chem. 1998 Dec 4;273(49):32910-9 PMID: 9830041
  75. Enforced expression of the GATA-2 transcription factor blocks normal hematopoiesis.
    Blood. 1999 Jan 15;93(2):488-99 PMID: 9885210
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1432147100
Published
2003-07-22
Epub
2003-00-11
Pages
8811-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC166395
Subset
IM
Grants
NIDDK NIH HHS · R01 DK050107 · United States
NIDDK NIH HHS · R37 DK050107 · United States
NIDDK NIH HHS · DK50107 · United States
External Links
PubMed source DOI: 10.1073/pnas.1432147100 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2