Howard Hughes Medical Institute, Molecular and Cell Biology Department, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell. 2011 Sep 2;146(5):720-31. doi: 10.1016/j.cell.2011.08.005.
Deciphering the molecular basis of pluripotency is fundamental to our understanding of development and embryonic stem cell function. Here, we report that TAF3, a TBP-associated core promoter factor, is highly enriched in ES cells. In this context, TAF3 is required for endoderm lineage differentiation and prevents premature specification of neuroectoderm and mesoderm. In addition to its role in the core promoter recognition complex TFIID, genome-wide binding studies reveal that TAF3 localizes to a subset of chromosomal regions bound by CTCF/cohesin that are selectively associated with genes upregulated by TAF3. Notably, CTCF directly recruits TAF3 to promoter distal sites and TAF3-dependent DNA looping is observed between the promoter distal sites and core promoters occupied by TAF3/CTCF/cohesin. Together, our findings support a new role of TAF3 in mediating long-range chromatin regulatory interactions that safeguard the finely-balanced transcriptional programs underlying pluripotency.
解析多能性的分子基础对于我们理解发育和胚胎干细胞功能至关重要。在这里，我们报告 TAF3，一种 TBP 相关的核心启动子因子，在 ES 细胞中高度富集。在这种情况下，TAF3 是内胚层谱系分化所必需的，可防止神经外胚层和中胚层的过早特化。除了在核心启动子识别复合物 TFIID 中的作用外，全基因组结合研究表明 TAF3 定位于由 CTCF/黏合蛋白结合的一组染色体区域，这些区域与 TAF3 上调的基因选择性相关。值得注意的是，CTCF 直接招募 TAF3 到启动子远端位点，并且在 TAF3/CTCF/黏合蛋白占据的启动子远端位点和核心启动子之间观察到 TAF3 依赖性 DNA 环化。总之，我们的研究结果支持 TAF3 在介导长距离染色质调控相互作用中的新作用，这些相互作用可确保多能性的精细平衡转录程序。
