Ho Lena, Jothi Raja, Ronan Jehnna L, Cui Kairong, Zhao Keji, Crabtree Gerald R
Programs in Immunology, Stanford University, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5187-91. doi: 10.1073/pnas.0812888106. Epub 2009 Mar 11.
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.
独特的SWI/SNF样ATP依赖性染色质重塑esBAF复合物对于小鼠胚胎干细胞(ES细胞)的维持和多能性不可或缺[Ho L等人(2009年)《美国国家科学院院刊》10.1073/pnas.0812889106]。为了了解这些复合物在ES细胞中发挥作用的潜在机制,我们使用ChIP-Seq技术对核心ATP酶亚基Brg进行了全基因组高分辨率定位。我们发现,以Brg为代表的esBAF与编码核心ES转录调控元件(包括多梳蛋白家族蛋白)的基因结合。在全基因组范围内,esBAF与转录因子Oct4、Sox2和Nanog广泛共定位,并在其靶基因处与Oct4和Sox2表现出不同的功能相互作用。令人惊讶的是,未观察到以Suz12为代表的esBAF与PRC2复合物有明显的共定位。最后,esBAF在全基因组范围内与Stat3和Smad1共定位,这与它在LIF和BMP信号通路中对维持自我更新的直接关键作用一致。综上所述,我们的研究表明,esBAF是核心多能性转录网络的重要组成部分,也可能是LIF和BMP信号通路中对维持自我更新和多能性至关重要的关键组成部分。