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

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.

Pubmed ID: 21596310


  • 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


Molecular cell

Publication Data

May 20, 2011

Associated Grants

  • Agency: NHGRI NIH HHS, Id: 1U54HG004558
  • Agency: NCI NIH HHS, Id: CA45250
  • Agency: NIGMS NIH HHS, Id: GM-64844
  • Agency: NCI NIH HHS, Id: P30 CA08748
  • Agency: NIGMS NIH HHS, Id: R01 GM064844
  • Agency: NIGMS NIH HHS, Id: R01 GM064844-05
  • Agency: NIGMS NIH HHS, Id: R01 GM064844-06
  • Agency: NIGMS NIH HHS, Id: R01 GM064844-07
  • Agency: NIGMS NIH HHS, Id: R01 GM064844-08
  • Agency: NIGMS NIH HHS, Id: R01 GM064844-09
  • Agency: NIGMS NIH HHS, Id: R01 GM064844-10
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Chromatin
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • HEK293 Cells
  • Histones
  • Humans
  • Nuclear Proteins
  • Polycomb-Group Proteins
  • Repressor Proteins
  • Transcription Factors
  • Ubiquitination