FOG-1-mediated recruitment of NuRD is required for cell lineage re-enforcement during haematopoiesis

Zhiguang Gao, Zan Huang, Harold E. Olivey, Sandeep Gurbuxani, John D. Crispino, Eric C. Svensson

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The transcriptional co-factor Friend of GATA1 (FOG-1) has been shown to interact with subunits of the nucleosome remodelling and histone deacetylase (NuRD) complex through a specific motif located at its N-terminus. To test the importance of FOG-1/NuRD interaction for haematopoiesis in vivo, we generated mice with a mutation that specifically disrupts FOG-1/NuRD interaction (FOG-1 R3K5A). Homozygous FOG-1 R3K5A mice were found to have splenomegaly, extramedullary erythropoiesis, granulocytosis and thrombocytopaenia secondary to a block in megakaryocyte maturation. FOG-1 R3K5A/R3K5A megakaryocytes and erythroid progenitors expressed increased levels of GATA2, showing that FOG-1/NuRD interaction is required for the earlier described GATA Switch. In addition, ablation of FOG-1/NuRD interaction led to inappropriate expression of mast cell and eosinophil-specific genes in the megakaryocyte and erythroid lineages. Chromatin immunoprecipitation experiments revealed that the NuRD complex was not properly recruited to a mast cell gene promoter in FOG-1 R3K5A/R3K5A megakaryocytes, suggesting that FOG-1/NuRD interaction is required for the direct suppression of mast cell gene expression. Taken together, these results underscore the importance of the FOG-1/NuRD interaction for the re-enforcement of lineage commitment during erythropoiesis and megakaryopoiesis in vivo.

Original languageEnglish (US)
Pages (from-to)457-468
Number of pages12
JournalEMBO Journal
Volume29
Issue number2
DOIs
StatePublished - Jan 2010

Keywords

  • Chromatin remodelling
  • Haematopoiesis
  • Lineage commitment
  • Mast cell
  • Transcriptional repression

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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