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PMID: 21596310 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

L3MBTL2 protein acts in concert with PcG protein-mediated monoubiquitination of H2A to establish a repressive chromatin structure.

Molecular cell ·Vol. 42 ·No. 4 ·2011-05-20 ·Pages 438-50

Trojer P, Cao AR, Gao Z, Li Y, Zhang J, Xu X, Li G, Losson R, Erdjument-Bromage H, Tempst P, Farnham PJ, Reinberg D

Abstract

We have identified human MBT domain-containing protein L3MBTL2 as an integral component of a protein complex that we termed Polycomb repressive complex 1 (PRC1)-like 4 (PRC1L4), given the copresence of PcG proteins RING1, RING2, and PCGF6/MBLR. PRC1L4 also contained E2F6 and CBX3/HP1γ, known to function in transcriptional repression. PRC1L4-mediated repression necessitated L3MBTL2 that compacted chromatin in a histone modification-independent manner. Genome-wide location analyses identified several hundred genes simultaneously bound by L3MBTL2 and E2F6, preferentially around transcriptional start sites that exhibited little overlap with those targeted by other E2Fs or by L3MBTL1, another MBT domain-containing protein that interacts with RB1. L3MBTL2-specific RNAi resulted in increased expression of target genes that exhibited a significant reduction in H2A lysine 119 monoubiquitination. Our findings highlight a PcG/MBT collaboration that attains repressive chromatin without entailing histone lysine methylation marks.

MeSH Terms
Chromatin/metabolism Gene Expression Regulation Genome-Wide Association Study HEK293 Cells Histones/genetics,metabolism Humans Nuclear Proteins/genetics,metabolism Polycomb-Group Proteins Repressor Proteins/genetics,metabolism Transcription Factors/genetics,metabolism Ubiquitination
Chemicals
Chromatin Histones L3MBTL2 protein, human Nuclear Proteins Polycomb-Group Proteins Repressor Proteins Transcription Factors histone H2A.F-Z
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Trojer Patrick
Howard Hughes Medical Institute, NYU Medical School, 522 First Avenue, New York, NY 10016, USA.
Cao Alina R
Gao Zhonghua
Li Yan
Zhang Jin
Xu Xiaoqin
Li Guohong
Losson Regine
Erdjument-Bromage Hediye
Tempst Paul
Farnham Peggy J
Reinberg Danny
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2011.04.004
Published
2011-05-20
Pages
438-50
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3142354
Subset
IM
Grants
NHGRI NIH HHS · U54 HG004558 · United States
NIGMS NIH HHS · R01 GM064844-07 · United States
NCI NIH HHS · CA45250 · United States
NIGMS NIH HHS · GM-64844 · United States
NHGRI NIH HHS · 1U54HG004558 · United States
NCI NIH HHS · P30 CA008748 · United States
NIGMS NIH HHS · R01 GM064844-10 · United States
NIGMS NIH HHS · R01 GM064844-05 · United States
NIGMS NIH HHS · R01 GM064844-06 · United States
NIGMS NIH HHS · R01 GM064844-08 · United States
NIGMS NIH HHS · R01 GM064844-09 · United States
NCI NIH HHS · P30 CA08748 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM064844 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2011.04.004 PMC Full Text View journal details
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