H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence

Chicas, A., Kapoor, A., Wang, X. W., Aksoy, O., Evertts, A. G., Zhang, M. Q., Garcia, B. A., Bernstein, E., Lowe, S. W. (June 2012) H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence. Proceedings of the National Academy of Sciences of the United States of America, 109 (23). pp. 8971-8976. ISSN 0027-8424

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URL: http://www.ncbi.nlm.nih.gov/pubmed/22615382
DOI: 10.1073/pnas.1119836109

Abstract

Cellular senescence is a tumor-suppressive program that involves chromatin reorganization and specific changes in gene expression that trigger an irreversible cell-cycle arrest. Here we combine quantitative mass spectrometry, ChIP deep-sequencing, and functional studies to determine the role of histone modifications on chromatin structure and gene-expression alterations associated with senescence in primary human cells. We uncover distinct senescence-associated changes in histone-modification patterns consistent with a repressive chromatin environment and link the establishment of one of these patterns-loss of H3K4 methylation-to the retinoblastoma tumor suppressor and the H3K4 demethylases Jarid1a and Jarid1b. Our results show that Jarid1a/b-mediated H3K4 demethylation contributes to silencing of retinoblastoma target genes in senescent cells, suggesting a mechanism by which retinoblastoma triggers gene silencing. Therefore, we link the Jarid1a and Jarid1b demethylases to a tumor-suppressor network controlling cellular senescence.

Item Type: Paper
Uncontrolled Keywords: H3K4me3 histone demethylase cells genome differentiation tumorigenesis binding cancer
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
organs, tissues, organelles, cell types and functions > cell types and functions
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 > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation > histone methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:
Communities: CSHL labs > Lowe lab
Watson School > Publications
Depositing User: Matt Covey
Date: 5 June 2012
Date Deposited: 31 Jan 2013 20:20
Last Modified: 22 Dec 2017 17:16
PMCID: PMC3384172
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26923

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