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

   

Authors:	Chicas, A.; Kapoor, A.; Wang, X.; Aksoy, O.; Evertts, A. G.; Zhang, M. Q.; Garcia, B. A.; Bernstein, E.; Lowe, S. W.
Article Title:	H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence
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.
Keywords:	unclassified drug; methylation; mass spectrometry; cell cycle; cell line; genetic vectors; nuclear proteins; gene expression regulation; reverse transcriptase polymerase chain reaction; chromatin; chromatin immunoprecipitation; immunoblotting; gene silencing; retinoblastoma protein; repressor proteins; histones; cell aging; retroviridae; sequence analysis, dna; demethylation; histone demethylase; h3k4me3; high-throughput nucleotide sequencing; jarid1a demethylase; jarid1b demethylase; protein h3k4; jumonji domain-containing histone demethylases; retinoblastoma-binding protein 2
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	109
Issue:	23
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	2012-06-05
Start Page:	8971
End Page:	8976
Language:	English
DOI:	10.1073/pnas.1119836109
PROVIDER:	scopus
PMCID:	PMC3384172
PUBMED:	22615382
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84861868041&partnerID=40&md5=b93fce74ac3916991fe12aa006e8010f
Notes:	--- - "Export Date: 2 July 2012" - "CODEN: PNASA" - "Source: Scopus"

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