title: L3MBTL2 protein acts in concert with PcG protein-mediated monoubiquitination of H2A to establish a repressive chromatin structure.
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.
authors: Howard Hughes Medical Institute, NYU Medical School, 522 First Avenue, New York, NY 10016, USA.
authors: Patrick
authors: P
authors: Trojer
authors: Alina R
authors: AR
authors: Cao
authors: Zhonghua
authors: Z
authors: Gao
authors: Yan
authors: Y
authors: Li
authors: Jin
authors: J
authors: Zhang
authors: Xiaoqin
authors: X
authors: Xu
authors: Guohong
authors: G
authors: Li
authors: Regine
authors: R
authors: Losson
authors: Hediye
authors: H
authors: Erdjument-Bromage
authors: Paul
authors: P
authors: Tempst
authors: Peggy J
authors: PJ
authors: Farnham
authors: Danny
authors: D
authors: Reinberg
references: Nucleic Acids Res. 2008 Jun;36(11):3590-9
references: 18460542
references: EMBO Rep. 2002 Jul;3(7):695-700
references: 12101104
references: Nature. 2009 Oct 8;461(7265):762-7
references: 19767730
references: Cell. 2007 Mar 9;128(5):1003-12
references: 17350582
references: Semin Cell Dev Biol. 2010 Apr;21(2):221-30
references: 19778625
references: Mol Cell. 2004 Oct 8;16(1):93-105
references: 15469825
references: Nat Cell Biol. 2007 Dec;9(12):1428-35
references: 18037880
references: Methods. 2006 Dec;40(4):331-8
references: 17101445
references: J Biol Chem. 2006 Aug 11;281(32):22537-44
references: 16751658
references: PLoS One. 2009 Oct 20;4(10):e7274
references: 19841675
references: J Biol Chem. 2003 Nov 21;278(47):46968-73
references: 12952983
references: Cell. 2007 Jun 1;129(5):915-28
references: 17540172
references: Curr Opin Genet Dev. 2009 Apr;19(2):150-8
references: 19345089
references: Genes Dev. 2008 Jan 1;22(1):37-49
references: 18172164
references: Cell. 2010 Jun 11;141(6):970-81
references: 20550933
references: J Mol Biol. 2008 Oct 24;382(5):1107-12
references: 18706910
references: Dev Cell. 2004 Nov;7(5):663-76
references: 15525528
references: EMBO J. 2009 Jul 8;28(13):1965-77
references: 19494831
references: Annu Rev Genet. 2009;43:559-99
references: 19886812
references: Nucleic Acids Res. 1983 Mar 11;11(5):1475-89
references: 6828386
references: J Biol Chem. 2005 Dec 16;280(50):41380-6
references: 16236716
references: Nature. 2004 Oct 14;431(7010):873-8
references: 15386022
references: Nat Struct Mol Biol. 2007 Dec;14(12):1229-30
references: 18026117
references: Mol Cell. 2007 Nov 30;28(4):677-91
references: 18042461
references: Genome Res. 2007 Nov;17(11):1550-61
references: 17908821
references: J Biol Chem. 2005 Jan 14;280(2):1199-208
references: 15536069
references: Structure. 2003 Jul;11(7):775-89
references: 12842041
references: Cell. 2007 Mar 9;128(5):877-87
references: 17320162
references: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2468-73
references: 12589020
references: Mol Cell. 2010 May 14;38(3):452-64
references: 20471950
references: Oncogene. 2007 Mar 15;26(12):1714-22
references: 17001316
references: Mol Cell. 2005 Dec 22;20(6):845-54
references: 16359901
references: Science. 2004 Nov 26;306(5701):1574-7
references: 15567868
references: Mol Cell Proteomics. 2007 May;6(5):820-34
references: 17296600
references: Genes Dev. 2004 Dec 1;18(23):2941-51
references: 15574595
references: J Biol Chem. 2003 Oct 24;278(43):42466-76
references: 12909625
references: Development. 2000 Dec;127(23):5093-100
references: 11060235
references: Curr Biol. 2005 Jun 7;15(11):1051-7
references: 15936277
references: Nat Rev Mol Cell Biol. 2007 Dec;8(12):983-94
references: 18037899
references: Cell. 2006 May 19;125(4):703-17
references: 16713563
references: Nucleic Acids Res. 2009 Apr;37(7):2204-10
references: 19233876
references: Nat Struct Mol Biol. 2007 Nov;14(11):1025-1040
references: 17984965
references: Trends Cell Biol. 2009 Dec;19(12):692-704
references: 19889541
references: Science. 2002 May 10;296(5570):1132-6
references: 12004135
references: Mol Cell. 2008 Nov 21;32(4):503-18
references: 19026781
references: EMBO Rep. 2007 Nov;8(11):1031-7
references: 17932512
references: Cell Cycle. 2008 Mar 1;7(5):578-85
references: 18256536
references: Mol Cell. 2008 Jan 18;29(1):69-80
references: 18206970