Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes

Many mammalian SWI/SNF complexes use Brahma‐related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes for transcription regulation. In several mesenchymal cells and tissues, expression of a defective Brg1 protein negates the normal activity of the SWI/SNF complex and delays or blocks differentiation. To investigate the role of SWI/SNF complexes during myelopoiesis, we stably expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage. Forced expression of dnBrg1 in IL‐3‐dependent murine 32Dcl3 myeloid progenitor cells results in a profound delay in the granulocyte‐colony stimulating factor (G‐CSF) induced granulocytic maturation. These cells also exhibit a significant decrease in the expression of both CD11b and Gr‐1 surface receptors, which are normally upregulated during granulopoiesis, and show sustained expression of myeloperoxidase, which is synthesized primarily during the promyelocytic (blast) stage of myeloid development. Thus, dnBrg1 expression causes a developmental block at the promyelocytic/metamyelocytic stage of myeloid differentiation. Our findings indicate that the normal chromatin remodeling function of Brg1 is necessary for the G‐CSF dependent differentiation of myeloid cells towards the granulocytic lineage. This dependency on Brg1 may reflect a stringent requirement for chromatin remodeling at a critical stage of hematopoietic cell maturation. © 2005 Wiley‐Liss, Inc.