| Literature DB >> 21477851 |
Yen-Sin Ang1, Su-Yi Tsai, Dung-Fang Lee, Jonathan Monk, Jie Su, Kajan Ratnakumar, Junjun Ding, Yongchao Ge, Henia Darr, Betty Chang, Jianlong Wang, Michael Rendl, Emily Bernstein, Christoph Schaniel, Ihor R Lemischka.
Abstract
The embryonic stem (ES) cell transcriptional and chromatin-modifying networks are critical for self-renewal maintenance. However, it remains unclear whether these networks functionally interact and, if so, what factors mediate such interactions. Here, we show that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively correlates with the undifferentiated state and is a regulator of ES cell self-renewal. We demonstrate that Wdr5, an "effector" of H3K4 methylation, interacts with the pluripotency transcription factor Oct4. Genome-wide protein localization and transcriptome analyses demonstrate overlapping gene regulatory functions between Oct4 and Wdr5. The Oct4-Sox2-Nanog circuitry and trxG cooperate in activating transcription of key self-renewal regulators, and furthermore, Wdr5 expression is required for the efficient formation of induced pluripotent stem (iPS) cells. We propose an integrated model of transcriptional and epigenetic control, mediated by select trxG members, for the maintenance of ES cell self-renewal and somatic cell reprogramming.Entities:
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Year: 2011 PMID： 21477851 PMCID： PMC3097468 DOI： 10.1016/j.cell.2011.03.003
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582