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The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination.

The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination.

Authors :
Yao, Xiao
Tang, Zhanyun
Fu, Xing
Yin, Jingwen
Liang, Yan
Li, Chonghui
Li, Huayun
Tian, Qing
Roeder, Robert G
Wang, Gang
Source :
EMBO Journal. 12/2/2015, Vol. 34 Issue 23, p2885-2902. 18p.
Publication Year :
2015

Abstract

The Mediator complex orchestrates multiple transcription factors with the Pol II apparatus for precise transcriptional control. However, its interplay with the surrounding chromatin remains poorly understood. Here, we analyze differential histone modifications between WT and MED23-/- (KO) cells and identify H2B mono-ubiquitination at lysine 120 (H2Bub) as a MED23-dependent histone modification. Using tandem affinity purification and mass spectrometry, we find that MED23 associates with the RNF20/40 complex, the enzyme for H2Bub, and show that this association is critical for the recruitment of RNF20/40 to chromatin. In a cell-free system, Mediator directly and substantially increases H2Bub on recombinant chromatin through its cooperation with RNF20/40 and the PAF complex. Integrative genome-wide analyses show that MED23 depletion specifically reduces H2Bub on a subset of MED23-controlled genes. Importantly, MED23-coupled H2Bub levels are oppositely regulated during myogenesis and lung carcinogenesis. In sum, these results establish a mechanistic link between the Mediator complex and a critical chromatin modification in coordinating transcription with cell growth and differentiation. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02614189
Volume :
34
Issue :
23
Database :
Academic Search Index
Journal :
EMBO Journal
Publication Type :
Academic Journal
Accession number :
111519685
Full Text :
https://doi.org/10.15252/embj.201591279