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

Vradii, D; Wagner S.; Doan, DN; Nickerson, JA; Montecino, M.; Lian, JB; Stein, JL; van Wijnen, AJ; Imbalzano, AN; Stein, GS

Abstract

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 32Dc13 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.

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Título según WOS: Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes
Título según SCOPUS: Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes
Título de la Revista: JOURNAL OF CELLULAR PHYSIOLOGY
Volumen: 206
Número: 1
Editorial: WILEY-BLACKWELL
Fecha de publicación: 2006
Página de inicio: 112
Página final: 118
Idioma: English
URL: http://doi.wiley.com/10.1002/jcp.20432
DOI:

10.1002/jcp.20432

Notas: ISI, SCOPUS