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

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 .