Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence

Narita, M., Nunez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., Lowe, S. W. (2003) Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell, 113 (6). pp. 703-716. ISSN 0092-8674

URL: http://www.ncbi.nlm.nih.gov/pubmed/12809602
DOI: 10.1016/S0092-8674(03)00401-X

Abstract

Cellular senescence is an extremely stable form of cell cycle arrest that limits the proliferation of damaged cells and may act as a natural barrier to cancer progression. In this study, we describe a distinct heterochromatic structure that accumulates in senescent human fibroblasts, which we designated senescence-associated heterochromatic foci (SAHF). SAHF formation coincides with the recruitment of heterochromatin proteins and the retinoblastoma (Rb) tumor suppressor to E2F-responsive promoters and is associated with the stable repression of E2F target genes. Notably, both SAHF formation and the silencing of E2F target genes depend on the integrity of the Rb pathway and do not occur in reversibly arrested cells. These results provide a molecular explanation for the stability of the senescent state, as well as new insights into the action of Rb as a tumor suppressor.

Item Type: Paper
Uncontrolled Keywords: HUMAN DIPLOID FIBROBLASTS Human diploid fibroblasts HUMAN TUMOR CELLS Human tumor cells HISTONE H3 Histone h3 IN VIVO in vivo ONCOGENIC RAS Oncogenic ras REPLICATIVE SENESCENCE Replicative senescence PREMATURE SENESCENCE Premature senescence HP1 hp1 PROTEINS Proteins X CHROMOSOME x chromosome G 1 CONTROL G 1 control
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics > heterochromatin
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > suppressor
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Lowe lab
CSHL labs > Spector lab
Depositing User: Editor Margaret Fantz
Date Deposited: 10 Apr 2012 19:27
Last Modified: 29 Jan 2015 15:43
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26131

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