PMID- 17332741
OWN - NLM
STAT- MEDLINE
DCOM- 20070724
LR  - 20191217
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 26
IP  - 6
DP  - 2007 Mar 21
TI  - Bypass of senescence by the polycomb group protein CBX8 through direct binding to 
      the INK4A-ARF locus.
PG  - 1637-48
AB  - The Polycomb group (PcG) proteins are essential for embryogenesis, and their 
      expression is often found deregulated in human cancer. The PcGs form two major 
      protein complexes, called polycomb repressive complexes 1 and 2 (PRC1 and PRC2) 
      whose function is to maintain transcriptional repression. Here, we demonstrate 
      that the chromodomain-containing protein, CBX8, which is part of one of the PRC1 
      complexes, regulates proliferation of diploid human and mouse fibroblasts through 
      direct binding to the INK4A-ARF locus. Furthermore, we demonstrate that CBX8 is 
      limiting for the regulation of INK4A-ARF, and that ectopic expression of CBX8 
      leads to repression of the Ink4a-Arf locus and bypass of senescence, leading to 
      cellular immortalization. Gene expression and location analysis demonstrate that 
      besides the INK4A-ARF locus, CBX8 also regulates a number of other genes 
      important for cell growth and survival. On the basis of these results, we 
      conclude that CBX8 is an essential component of one of the PRC1 complexes, which 
      directly regulate the expression of numerous target genes, including the 
      INK4A-ARF locus, involved in cell-fate decisions.
FAU - Dietrich, Nikolaj
AU  - Dietrich N
AD  - Centre for Epigenetics and Biotech Research & Innovation Centre (BRIC), 
      University of Copenhagen, Copenhagen, Denmark.
FAU - Bracken, Adrian P
AU  - Bracken AP
FAU - Trinh, Emmanuelle
AU  - Trinh E
FAU - Schjerling, Charlotte K
AU  - Schjerling CK
FAU - Koseki, Haruhiko
AU  - Koseki H
FAU - Rappsilber, Juri
AU  - Rappsilber J
FAU - Helin, Kristian
AU  - Helin K
FAU - Hansen, Klaus H
AU  - Hansen KH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070301
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (BMI1 protein, human)
RN  - 0 (CBX8 protein, human)
RN  - 0 (Chromatin)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Polycomb-Group Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - EC 2.3.2.27 (Cbx8 protein, mouse)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
SB  - IM
MH  - Animals
MH  - *Cell Proliferation
MH  - Cellular Senescence/genetics/*physiology
MH  - Chromatin/*metabolism
MH  - Chromatin Immunoprecipitation
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics/metabolism
MH  - Fibroblasts
MH  - Flow Cytometry
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/genetics/*physiology
MH  - Humans
MH  - Mice
MH  - Microscopy, Fluorescence
MH  - Mitochondrial Membrane Transport Proteins
MH  - Nuclear Proteins/metabolism
MH  - Polycomb Repressive Complex 1
MH  - Polycomb-Group Proteins
MH  - Proto-Oncogene Proteins/metabolism
MH  - Repressor Proteins/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC1829390
EDAT- 2007/03/03 09:00
MHDA- 2007/07/25 09:00
PMCR- 2008/03/21
CRDT- 2007/03/03 09:00
PHST- 2006/09/01 00:00 [received]
PHST- 2007/02/06 00:00 [accepted]
PHST- 2007/03/03 09:00 [pubmed]
PHST- 2007/07/25 09:00 [medline]
PHST- 2007/03/03 09:00 [entrez]
PHST- 2008/03/21 00:00 [pmc-release]
AID - 7601632 [pii]
AID - 10.1038/sj.emboj.7601632 [doi]
PST - ppublish
SO  - EMBO J. 2007 Mar 21;26(6):1637-48. doi: 10.1038/sj.emboj.7601632. Epub 2007 Mar 
      1.