Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Cell. 2013 Jan 17;152(1-2):144-56. doi: 10.1016/j.cell.2012.12.015. Epub 2012 Dec 27.
Enhancers play a central role in precisely regulating the expression of developmentally regulated genes. However, the machineries required for enhancer-promoter communication have remained largely unknown. We have found that Ell3, a member of the Ell (eleven-nineteen lysine-rich leukemia gene) family of RNA Pol II elongation factors, occupies enhancers in embryonic stem cells. Ell3's association with enhancers is required for setting up proper Pol II occupancy at the promoter-proximal regions of developmentally regulated genes and for the recruitment of the super elongation complex (SEC) to these loci following differentiation signals. Furthermore, Ell3 binding to inactive or poised enhancers is essential for stem cell specification. We have also detected the presence of Pol II and Ell3 in germ cell nuclei. These findings raise the possibility that transcription factors could prime gene expression by marking enhancers in ES cells or even as early as in the germ cell state.
增强子在精确调控发育调控基因的表达方面起着核心作用。然而，增强子-启动子通讯所需的机制在很大程度上仍是未知的。我们发现，Ell3 是 RNA Pol II 延伸因子 Ell（eleven-nineteen lysine-rich leukemia gene）家族的成员，它在胚胎干细胞中占据增强子的位置。Ell3 与增强子的结合对于在发育调控基因的启动子近端区域建立适当的 Pol II 占据以及在分化信号后将超级延伸复合物 (SEC) 招募到这些基因座是必需的。此外，Ell3 与非活性或静止增强子的结合对于干细胞的特化是必不可少的。我们还在生殖细胞核中检测到了 Pol II 和 Ell3 的存在。这些发现提出了这样一种可能性，即转录因子可以通过在 ES 细胞中标记增强子，甚至早在生殖细胞状态下，就可以启动基因表达。
