Institute of Cell Biology, School of Medicine, Shandong University, Shandong 250100, China.
Cell Stem Cell. 2012 Aug 3;11(2):163-78. doi: 10.1016/j.stem.2012.04.023.
Pluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential. They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs.
多能胚胎干细胞 (ESCs) 保持自我更新和对分化信号快速响应的潜力。这两个 ESC 特征都受到表观遗传调控。在这里，我们表明组蛋白乙酰转移酶 Mof 在维持 ESC 自我更新和多能性方面发挥着重要作用。Mof 缺失的 ESCs 失去了特征性形态、碱性磷酸酶 (AP) 染色和分化潜能。它们还表现出核心转录因子 Nanog、Oct4 和 Sox2 的异常表达。重要的是，Mof 缺失 ESC 的表型可以部分被 Nanog 过表达抑制，这支持了 Mof 在 ESCs 中作为 Nanog 的上游调节剂的观点。全基因组 ChIP-seq 和转录组分析进一步表明，Mof 是 ESC 核心转录网络的一个组成部分，并且 Mof 为各种发育程序的基因做好准备。Mof 还需要 Wdr5 的募集和关键调控位点处的 H3K4 甲基化，突出了 ESCs 中各种染色质调节剂的复杂性和相互关联性。
