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.

• Authors: Ping Zhu, Wenlai Zhou, Jianxun Wang, Janusz Puc, Kenneth A Ohgi, Hediye Erdjument-Bromage, Paul Tempst, Christopher K Glass, Michael G Rosenfeld
• Journal: Molecular cell (Mol Cell) Vol. 27 Issue 4 Pg. 609-21 (Aug 17 2007) ISSN: 1097-2765 [Print] United States
• PMID: 17707232 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AR protein, human
• Androgens
• DNA-Binding Proteins
• Histones
• MYSM1 protein, human
• Nucleosomes
• Receptors, Androgen
• Trans-Activators
• Transcription Factors
• Ubiquitins
• chromatin conjugate protein A24
• Histone Acetyltransferases
• Ubiquitin-Specific Proteases

Topics

• Acetylation (drug effects)
• Androgens (pharmacology)
• Animals
• Cell Line
• Chromatography, Affinity
• DNA-Binding Proteins (isolation & purification, metabolism)
• Gene Expression Regulation (drug effects)
• Histone Acetyltransferases (metabolism)
• Histones (metabolism)
• Humans
• Mice
• Models, Genetic
• Nucleosomes (drug effects, metabolism)
• Phosphorylation (drug effects)
• Receptors, Androgen (metabolism)
• Signal Transduction (drug effects)
• Trans-Activators
• Transcription Factors (isolation & purification, metabolism)
• Transcription, Genetic (drug effects)
• Transcriptional Activation (drug effects)
• Ubiquitin-Specific Proteases
• Ubiquitins (metabolism)