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

EMBO J. 2010 Jan 20;29(2):457-68. doi: 10.1038/emboj.2009.368. Epub 2009 Dec 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromatin / metabolism
  • Erythroid Cells / cytology
  • Erythroid Cells / metabolism
  • Erythropoiesis
  • GATA2 Transcription Factor / genetics
  • GATA2 Transcription Factor / metabolism
  • Gene Expression Regulation
  • Granulocytes / cytology
  • Hematopoiesis*
  • Megakaryocytes / cytology
  • Megakaryocytes / metabolism
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
  • Mice
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Chromatin
  • GATA2 Transcription Factor
  • Gata2 protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • Zfpm1 protein, mouse
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex