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

The EMBO journal | Jan 20, 2010

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.

Pubmed ID: 19927129 RIS Download

Mesh terms: Animals | Cells, Cultured | Erythroid Cells | GATA1 Transcription Factor | Hematopoiesis | Megakaryocytes | Mi-2 Nucleosome Remodeling and Deacetylase Complex | Mice | Nuclear Proteins | Transcription Factors | Transcription, Genetic | Transcriptional Activation

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Associated grants

  • Agency: NHLBI NIH HHS, Id: HL064632
  • Agency: NHLBI NIH HHS, Id: U01 HL099656
  • Agency: NIDDK NIH HHS, Id: R01 DK058044
  • Agency: NIDDK NIH HHS, Id: DK58044
  • Agency: NHLBI NIH HHS, Id: R01 HL095675
  • Agency: NHLBI NIH HHS, Id: HL40387
  • Agency: NIDDK NIH HHS, Id: R37 DK058044
  • Agency: NHLBI NIH HHS, Id: R01 HL064632
  • Agency: NHLBI NIH HHS, Id: P01 HL040387
  • Agency: NIDDK NIH HHS, Id: R01 DK054937
  • Agency: NIDDK NIH HHS, Id: DK54937

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