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Research Article

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

Lena Ho, Raja Jothi, Jehnna L. Ronan, Kairong Cui, Keji Zhao, and Gerald R. Crabtree
PNAS March 31, 2009 106 (13) 5187-5191; https://doi.org/10.1073/pnas.0812888106
Lena Ho
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Raja Jothi
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Jehnna L. Ronan
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Kairong Cui
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Keji Zhao
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Gerald R. Crabtree
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  • For correspondence: crabtree@cmgm.stanford.edu
  1. Contributed by Gerald R. Crabtree, December 18, 2008

  2. ↵1L.H. and R.J. contributed equally to this work (received for review December 15, 2008)

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Abstract

Distinctive SWI/SNF-like ATP-dependent chromatin remodeling esBAF 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 Sox2 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.

Keywords:
  • BAF complexes
  • Brg
  • SWI/SNF ATP-dependent chromatin remodeling

Footnotes

  • 2To whom correspondence should be addressed. E-mail: crabtree{at}cmgm.stanford.edu
  • Author contributions: L.H., R.J., and G.R.C. designed research; L.H., R.J., and J.L.R. performed research; L.H., R.J., J.L.R., K.C., and K.Z. contributed new reagents/analytic tools; L.H. and R.J. analyzed data; and L.H. wrote the paper.

  • The authors declare no conflict of interest.

  • Data deposition: Primary sequencing and microarray data have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE14344).

  • This article contains supporting information online at www.pnas.org/cgi/content/full/0812888106/DCSupplemental.

  • Freely available online through the PNAS open access option.

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An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network
Lena Ho, Raja Jothi, Jehnna L. Ronan, Kairong Cui, Keji Zhao, Gerald R. Crabtree
Proceedings of the National Academy of Sciences Mar 2009, 106 (13) 5187-5191; DOI: 10.1073/pnas.0812888106

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An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network
Lena Ho, Raja Jothi, Jehnna L. Ronan, Kairong Cui, Keji Zhao, Gerald R. Crabtree
Proceedings of the National Academy of Sciences Mar 2009, 106 (13) 5187-5191; DOI: 10.1073/pnas.0812888106
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Proceedings of the National Academy of Sciences: 106 (13)
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