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Blood. 2014 Mar 13;123(11):1720-8. doi: 10.1182/blood-2013-02-483495. Epub 2014 Jan 29.

Essential role of BRG, the ATPase subunit of BAF chromatin remodeling complexes, in leukemia maintenance.

Author information

1
Institute for Research in Immunology and Cancer, Montreal, QC, Canada;

Abstract

In mammals, combinatorial assembly of alternative families of subunits confers functional specificity to adenosine triphosphate (ATP)-dependent SWI/SNF-like Brg/Brm-associated factor (BAF) chromatin remodeling complexes by creating distinct polymorphic surfaces for interaction with regulatory elements and DNA-binding factors. Although redundant in terms of biochemical activity, the core ATPase subunits, BRG/SMARCA4 and BRM/SMARCA2, are functionally distinct and may contribute to complex specificity. Here we show using quantitative proteomics that BAF complexes expressed in leukemia are specifically assembled around the BRG ATPase. Moreover, using a mouse model of acute myeloid leukemia, we demonstrate that BRG is essential for leukemia maintenance, as leukemic cells lacking BRG rapidly undergo cell-cycle arrest and apoptosis. Most importantly, we show that BRG is dispensable for the maintenance of immunophenotypic long-term repopulating hematopoietic stem cells, suggesting that adroit targeting of BRG in leukemia may have potent and specific therapeutic effects.

PMID:
24478402
PMCID:
PMC3954053
DOI:
10.1182/blood-2013-02-483495
[Indexed for MEDLINE]
Free PMC Article

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