A UTX-MLL4-p300 transcriptional regulatory network coordinately shapes active enhancer landscapes for eliciting transcription Journal Article

   

Authors:	Wang, S. P.; Tang, Z.; Chen, C. W.; Shimada, M.; Koche, R. P.; Wang, L. H.; Nakadai, T.; Chramiec, A.; Krivtsov, A. V.; Armstrong, S. A.; Roeder, R. G.
Article Title:	A UTX-MLL4-p300 transcriptional regulatory network coordinately shapes active enhancer landscapes for eliciting transcription
Abstract:	Enhancer activation is a critical step for gene activation. Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1+/H3K27ac+) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription. The UTX-MLL4 complex enhances p300-dependent H3K27 acetylation through UTX-dependent stimulation of p300 recruitment, while MLL4-mediated H3K4 monomethylation, reciprocally, requires p300 function. Importantly, MLL4-generated H3K4me1 further enhances p300-dependent transcription. This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an “active enhancer landscape” and defines a detailed mechanism for the joint deposition of H3K4me1 and H3K27ac. © 2017 Elsevier Inc.
Keywords:	histone methyltransferase; transcriptional activation; histone acetyltransferase; chromatin modification; active enhancer landscape; enhancer regulation; epigenetic crosstalk; mll4/kmt2d; p300/ep300; utx/hdm6a
Journal Title:	Molecular Cell
Volume:	67
Issue:	2
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	2017-07-20
Start Page:	308
End Page:	321.e6
Language:	English
DOI:	10.1016/j.molcel.2017.06.028
PROVIDER:	scopus
PUBMED:	28732206
PMCID:	PMC5574165
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85025130546&doi=10.1016%2fj.molcel.2017.06.028&partnerID=40&md5=7a03e6ed33ae774fc132739522051227
Notes:	Article -- Export Date: 2 August 2017 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/114182