4.8 Article

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

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.0812888106

关键词

BAF complexes; Brg; SWI/SNF ATP-dependent chromatin remodeling

资金

  1. Howard Hughes Medical Institute
  2. NIH [NS046789, Hd155391, A1060037]
  3. JDRF
  4. Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health
  5. Agency of Science, Technology and Research of Singapore

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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.

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