SWI/SNF-Brg1 Regulates Self-Renewal and Occupies Core Pluripotency-Related Genes in Embryonic Stem Cells

被引:190
作者
Kidder, Benjamin L. [2 ]
Palmer, Stephen [2 ]
Knott, Jason G. [1 ,2 ]
机构
[1] Michigan State Univ, Dept Anim Sci, Dev Epigenet Lab, E Lansing, MI 48824 USA
[2] EMD Serono Res Inst Inc, Rockland, MA USA
关键词
Epigenetics; Genomics; Microarray; Embryonic stem cells; Self-renewal; Pluripotent; CHROMATIN-REMODELING COMPLEX; DEVELOPMENTAL REGULATORS; ATPASE SUBUNIT; MOUSE CLONES; BRG1; EXPRESSION; DIFFERENTIATION; NANOG; OCT4; ABSENCE;
D O I
10.1634/stemcells.2008-0710
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The SWI/SNF-Brg1 chromatin remodeling protein plays critical roles in cell-cycle control and differentiation through regulation of gene expression. Loss of Brg1 in mice results in early embryonic lethality, and recent studies have implicated a role for Brg1 in somatic stem cell self-renewal and differentiation. However, little is known about Brg1 function in preimplantation embryos and embryonic stem (ES) cells. Here we report that Brg1 is required for ES cell self-renewal and pluripotency. RNA interference-mediated knockdown of Brg1 in blastocysts caused aberrant expression of Oct4 and Nanog. In ES cells, knockdown of Brg1 resulted in phenotypic changes indicative of differentiation, downregulation of self-renewal and pluripotency genes (e. g., Oct4, Sox2, Sall4, Rest), and upregulation of differentiation genes. Using genome-wide promoter analysis (chromatin immunoprecipitation) we found that Brg1 occupied the promoters of key pluripotency-related genes, including Oct4, Sox2, Nanog, Sall4, Rest, and Polycomb group (PcG) proteins. Moreover, Brg1 co-occupied a subset of Oct4, Sox2, Nanog, and PcG protein target genes. These results demonstrate an important role for Brg1 in regulating self-renewal and pluripotency in ES cells. STEM CELLS 2009; 27: 317-328
引用
收藏
页码:317 / 328
页数:12
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