An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network

被引:328
作者
Ho, Lena [4 ]
Jothi, Raja [6 ]
Ronan, Jehnna L. [5 ]
Cui, Kairong [6 ]
Zhao, Keji [6 ]
Crabtree, Gerald R. [1 ,2 ,3 ]
机构
[1] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA
[4] Stanford Univ, Program Immunol, Stanford, CA 94305 USA
[5] Stanford Univ, Program Canc Biol, Stanford, CA 94305 USA
[6] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
BAF complexes; Brg; SWI/SNF ATP-dependent chromatin remodeling; SELF-RENEWAL; ES CELLS; DEVELOPMENTAL REGULATORS; MOUSE; NANOG; DIFFERENTIATION; EXPRESSION; CIRCUITRY; POLYCOMB; OCT4;
D O I
10.1073/pnas.0812888106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Distinctive SWI/SNF-like ATP-dependent chromatin remodeling es-BAF complexes are indispensable for the maintenance and pluripotency of mouse embryonic stem (ES) cells [Ho L, et al. (2009) Proc Natl Acad Sci USA 10.1073/pnas.0812889106). To understand the mechanism underlying the roles of these complexes in ES cells, we performed high-resolution genome-wide mapping of the core ATPase subunit, Brg, using ChIP-Seq technology. We find that esBAF, as represented by Brg, binds to genes encoding components of the core ES transcriptional circuitry, including Polycomb group proteins. esBAF colocalizes extensively with transcription factors Oct4, Sox2 and Nanog genome-wide, and shows distinct functional interactions with Oct4 and SoxZ at its target genes. Surprisingly, no significant colocalization of esBAF with PRC2 complexes, represented by Suz12, is observed. Lastly, esBAF colocalizes with Stat3 and Smad1 genome-wide, consistent with a direct and critical role in LIF and BMP signaling for maintaining self-renewal. Taken together, our studies indicate that esBAF is an essential component of the core pluripotency transcriptional network, and might also be a critical component of the LIF and BMP signaling pathways essential for maintenance of self-renewal and pluripotency.
引用
收藏
页码:5187 / 5191
页数:5
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