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PMID: 19927129 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development.

The EMBO journal ·Vol. 29 ·No. 2 ·2010-01-20 ·Pages 442-56

Miccio A, Wang Y, Hong W, Gregory GD, Wang H, Yu X, Choi JK, Shelat S, Tong W, Poncz M, Blobel GA

Abstract

GATA transcription factors interact with FOG proteins to regulate tissue development by activating and repressing transcription. FOG-1 (ZFPM1), a co-factor for the haematopoietic factor GATA-1, binds to the NuRD co-repressor complex through a conserved N-terminal motif. Surprisingly, we detected NuRD components at both repressed and active GATA-1/FOG-1 target genes in vivo. In addition, while NuRD is required for transcriptional repression in certain contexts, we show a direct requirement of NuRD also for FOG-1-dependent transcriptional activation. Mice in which the FOG-1/NuRD interaction is disrupted display defects similar to germline mutations in the Gata1 and Fog1 genes, including anaemia and macrothrombocytopaenia. Gene expression analysis in primary mutant erythroid cells and megakaryocytes (MKs) revealed an essential function for NuRD during both the repression and activation of select GATA-1/FOG-1 target genes. These results show that NuRD is a critical co-factor for FOG-1 and underscore the versatile use of NuRD by lineage-specific transcription factors to activate and repress gene transcription in the appropriate cellular and genetic context.

MeSH Terms
Animals Cells, Cultured Erythroid Cells/cytology,metabolism GATA1 Transcription Factor/genetics,metabolism Hematopoiesis Megakaryocytes/cytology,metabolism Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism Mice Nuclear Proteins/genetics,metabolism Transcription Factors/genetics,metabolism Transcription, Genetic Transcriptional Activation
Chemicals
GATA1 Transcription Factor Gata1 protein, mouse Nuclear Proteins Transcription Factors Zfpm1 protein, mouse Mi-2 Nucleosome Remodeling and Deacetylase Complex
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Miccio Annarita
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Wang Yuhuan
Hong Wei
Gregory Gregory D
Wang Hongxin
Yu Xiang
Choi John K
Shelat Suresh
Tong Wei
Poncz Mortimer
Blobel Gerd A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2009.336
Published
2010-01-20
Epub
2009-00-19
Pages
442-56
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2824460
Subset
IM
Grants
NHLBI NIH HHS · HL064632 · United States
NHLBI NIH HHS · U01 HL099656 · United States
NIDDK NIH HHS · R01 DK058044 · United States
NIDDK NIH HHS · DK58044 · United States
NHLBI NIH HHS · R01 HL095675 · United States
NHLBI NIH HHS · HL40387 · United States
NIDDK NIH HHS · R37 DK058044 · United States
NHLBI NIH HHS · R01 HL064632 · United States
NIDDK NIH HHS · DK54937 · United States
NHLBI NIH HHS · P01 HL040387 · United States
NIDDK NIH HHS · R01 DK054937 · United States
External Links
PubMed source DOI: 10.1038/emboj.2009.336 PMC Full Text View journal details
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