An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network.
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.
Ho
Lena
L
Programs in Immunology, Stanford University, Stanford, CA 94305, USA.
Jothi
Raja
R
Ronan
Jehnna L
JL
Cui
Kairong
K
Zhao
Keji
K
Crabtree
Gerald R
GR
D000251:Adenosine Triphosphatases; D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology*; D053263:Gene Regulatory Networks; D023281:Genomics; D051379:Mice; D039904:Pluripotent Stem Cells; D011485:Protein Binding; D053606:Receptors, OSM-LIF / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; D053606:Receptors, OSM-LIF; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D052004:Bone Morphogenetic Protein Receptors; D000251:Adenosine Triphosphatases