| Literature DB >> 17707232 |
Ping Zhu1, Wenlai Zhou, Jianxun Wang, Janusz Puc, Kenneth A Ohgi, Hediye Erdjument-Bromage, Paul Tempst, Christopher K Glass, Michael G Rosenfeld.
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.Entities:
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Year: 2007 PMID： 17707232 PMCID： PMC2709280 DOI： 10.1016/j.molcel.2007.07.024
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970