Institute for Regenerative Medicine, Epigenetics Program, Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Science. 2011 May 20;332(6032):963-6. doi: 10.1126/science.1202845.
Transcriptionally silent genes can be marked by histone modifications and regulatory proteins that indicate the genes' potential to be activated. Such marks have been identified in pluripotent cells, but it is unknown how such marks occur in descendant, multipotent embryonic cells that have restricted cell fate choices. We isolated mouse embryonic endoderm cells and assessed histone modifications at regulatory elements of silent genes that are activated upon liver or pancreas fate choices. We found that the liver and pancreas elements have distinct chromatin patterns. Furthermore, the histone acetyltransferase P300, recruited via bone morphogenetic protein signaling, and the histone methyltransferase Ezh2 have modulatory roles in the fate choice. These studies reveal a functional "prepattern" of chromatin states within multipotent progenitors and potential targets to modulate cell fate induction.
转录沉默基因可以通过组蛋白修饰和调控蛋白来标记，这些修饰和蛋白表明基因具有被激活的潜力。这种标记已经在多能细胞中被识别出来，但在具有受限细胞命运选择的多能胚胎细胞中，这种标记是如何产生的还不清楚。我们分离了小鼠胚胎内胚层细胞，并评估了在肝脏或胰腺命运选择中被激活的沉默基因的调控元件上的组蛋白修饰。我们发现，肝脏和胰腺元件具有不同的染色质模式。此外，通过骨形态发生蛋白信号招募的乙酰转移酶 P300 和组蛋白甲基转移酶 Ezh2 在命运选择中具有调节作用。这些研究揭示了多能祖细胞内染色质状态的功能性“预模式”，以及潜在的调节细胞命运诱导的靶标。
