NuRD Mediates Activating and Repressive Functions of GATA-1 and FOG-1 During Blood Development

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2009 Nov 21

PMID 19927129

Citations 98

Authors

Annarita Miccio

Yuhuan Wang

Wei Hong

Gregory D Gregory

Hongxin Wang

Xiang Yu

John K Choi

Suresh Shelat

Wei Tong

Mortimer Poncz

Gerd A Blobel

Affiliations

Soon will be listed here.

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.

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