Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity in Pluripotency and Reprogramming

Junjun Ding, Xin Huang, Ningyi Shao, Hongwei Zhou, Dung Fang Lee, Francesco Faiola, Miguel Fidalgo, Diana Guallar, Arven Saunders, Pavel V. Shliaha, Hailong Wang, Avinash Waghray, Dmitri Papatsenko, Carlos Sánchez-Priego, Dan Li, Ye Yuan, Ihor R. Lemischka, Li Shen, Kevin Kelley, Haiteng DengXiaohua Shen, Jianlong Wang

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage-specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for the core pluripotency factors Oct4, Sox2, and Nanog. In this study, we sought to dissect the molecular control mechanism of SE activity in pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, we identified Tex10 as a key pluripotency factor that plays a functionally significant role in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation at SEs. Tex10 activity is also important for pluripotency and reprogramming in human cells. Our study therefore highlights Tex10 as a core component of the pluripotency network and sheds light on its role in epigenetic control of SE activity for cell fate determination.

Original languageEnglish
Pages (from-to)653-668
Number of pages16
JournalCell Stem Cell
Volume16
Issue number6
DOIs
StatePublished - 4 Jun 2015

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