Mark the transition: chromatin modifications and cell fate decision

Abstract

With their unique features of self-renewal and pluripotency, human embryonic stem (hES) cells are considered to be a nearly unlimited resource for research and clinical applications 1. Accordingly, the transcriptional network specifying and governing human ES cell identity has been extensively studied. OCT4, NANOG and SOX2 form a core transcriptional network that regulates itself as well as a number of target genes 2. This transcriptional network acts together with signaling pathways to maintain ES cell identity 3. Moreover, the last decade has seen tremendous advances in understanding the epigenetic mechanisms underlying ES cell self-renewal and pluripotency. It is believed that the so-called “bivalent” histone modification (promoters of many developmental genes that co-harbor the active H3K4me3 and the silencing H3K27me3 marks) is required for undifferentiated ES cells to be poised to quickly differentiate into certain lineages 2. Besides H3K4me3, recent studies have indicated that histone H3K4me1 and H3K27ac are the marks of active regulatory regions, such as promoters and enhancers, in the mammalian genome 4. Given that transcription factors, cofactors and chromatin modifications are enriched in these regulatory regions, it is important to investigate the role of H3K4me1 and H3K27ac in regulation of ES cell pluripotency and differentiation.