A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation Journal Article
| Authors: | Zhu, P.; Zhou, W.; Wang, J.; Puc, J.; Ohgi, K. A.; Erdjument-Bromage, H.; Tempst, P.; Glass, C. K.; Rosenfeld, M. G. |
| Article Title: | 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. © 2007 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; human cell; dna-binding proteins; protein function; proteins; protein analysis; animals; mice; ubiquitin protein ligase; cell line; protein interaction; transcription, genetic; enzyme activity; phosphorylation; transcription factors; gene expression regulation; gene activation; dna; transcription regulation; ubiquitination; prostate tumor; androgen receptor; models, genetic; receptors, androgen; histone h2a; histones; androgens; acetylation; ubiquitins; nucleosome; nucleosomes; chromatography, affinity; trans-activation (genetics); histone acetyltransferases; histone h1 |
| Journal Title: | Molecular Cell |
| Volume: | 27 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2007-08-17 |
| Start Page: | 609 |
| End Page: | 621 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2007.07.024 |
| PUBMED: | 17707232 |
| PROVIDER: | scopus |
| PMCID: | PMC2709280 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 54" - "Export Date: 17 November 2011" - "CODEN: MOCEF" - "Source: Scopus" |
