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A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation.


ABSTRACT: Deciphering the epigenetic "code" remains a central issue in transcriptional regulation. Here, we report the identification of a JAMM/MPN(+) domain-containing histone H2A deubiquitinase (2A-DUB, or KIAA1915/MYSM1) specific for monoubiquitinated H2A (uH2A) that has permitted delineation of a strategy for specific regulatory pathways of gene activation. 2A-DUB regulates transcription by coordinating histone acetylation and deubiquitination, and destabilizing the association of linker histone H1 with nucleosomes. 2A-DUB interacts with p/CAF in a coregulatory protein complex, with its deubiquitinase activity modulated by the status of acetylation of nucleosomal histones. Consistent with this mechanistic role, 2A-DUB participates in transcriptional regulation events in androgen receptor-dependent gene activation, and the levels of uH2A are dramatically decreased in prostate tumors, serving as a cancer-related mark. We suggest that H2A ubiquitination represents a widely used mechanism for many regulatory transcriptional programs and predict that various H2A ubiquitin ligases/deubiquitinases will be identified for specific cohorts of regulated transcription units.

SUBMITTER: Zhu P 

PROVIDER: S-EPMC2709280 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation.

Zhu Ping P   Zhou Wenlai W   Wang Jianxun J   Puc Janusz J   Ohgi Kenneth A KA   Erdjument-Bromage Hediye H   Tempst Paul P   Glass Christopher K CK   Rosenfeld Michael G MG  

Molecular cell 20070801 4


Deciphering the epigenetic "code" remains a central issue in transcriptional regulation. Here, we report the identification of a JAMM/MPN(+) domain-containing histone H2A deubiquitinase (2A-DUB, or KIAA1915/MYSM1) specific for monoubiquitinated H2A (uH2A) that has permitted delineation of a strategy for specific regulatory pathways of gene activation. 2A-DUB regulates transcription by coordinating histone acetylation and deubiquitination, and destabilizing the association of linker histone H1 wi  ...[more]

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