Document Detail

Binding of the retinoblastoma protein is not the determinant for stable repression of some E2F-regulated promoters in muscle cells.
MedLine Citation:
PMID:  18296649     Owner:  NLM     Status:  MEDLINE    
Permanent silencing of E2F-dependent genes is a hallmark of the irreversible cell cycle exit that characterizes terminally differentiated and senescent cells. The determinant of this silencing during senescence has been proposed to be the binding of the retinoblastoma protein Rb and the consequent methylation of H3K9. During ex vivo skeletal muscle differentiation, while most cells terminally differentiate and form myotubes, a subset of myoblasts remains quiescent and can be reinduced by growth factor stimulation to enter the cell cycle. Thus, differentiating cells are composed of two different populations: one in which E2F-dependent genes are permanently repressed and the other not. We observed that, in a manner reminiscent to senescent cells, permanent silencing of the E2F-dependent cdc6, dhfr, and p107 promoters in myotubes was associated with a specific increase in H3K9 trimethylation. To investigate the role of Rb in this process, we developed a reliable method to detect Rb recruitment by chromatin immunoprecipitation. Surprisingly, we observed that Rb was recruited to these promoters more efficiently in quiescent cells than in myotubes. Thus, our data indicate that during muscle differentiation, permanent silencing and H3K9 trimethylation of some E2F-dependent genes are not directly specified by Rb binding, in contrast to what is proposed for senescence.
Marie Vandromme; Catherine Chailleux; Fabrice Escaffit; Didier Trouche
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-22
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  6     ISSN:  1541-7786     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-13     Completed Date:  2008-06-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  418-25     Citation Subset:  IM    
Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération, Centre National de la Recherche Scientifique, Université Paul Sabatier, Toulouse Cedex, France.
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MeSH Terms
Cell Aging
Cell Cycle
Cell Differentiation
Cell Line
Chromatin / metabolism
E2F Transcription Factors / metabolism*
Gene Amplification
Muscle, Skeletal / cytology,  physiology*
Myoblasts / cytology,  physiology*
Promoter Regions, Genetic*
RNA / genetics,  isolation & purification
Retinoblastoma Protein / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/Chromatin; 0/E2F Transcription Factors; 0/Retinoblastoma Protein; 63231-63-0/RNA

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