USP10 deubiquitylates the histone variant H2A.Z and both are required for androgen receptor-mediated gene activation
Open Access
- 17 January 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 39 (9), 3529-3542
- https://doi.org/10.1093/nar/gkq1352
Abstract
H2A.Z, a variant of H2A, is found at the promoters of inducible genes in both yeast and higher eukaryotes. However, its role in transcriptional regulation is complex since it has been reported to function both as a repressor and activator. We have previously found that mono-ubiquitylation of H2A.Z is linked to transcriptional silencing. Here, we provide new evidence linking H2A.Z deubiquitylation to transcription activation. We found that H2A.Z and ubiquitin-specific protease 10 (USP10) are each required for transcriptional activation of the androgen receptor (AR)-regulated PSA and KLK3 genes. USP10 directly deubiquitylates H2A.Z in vitro and in vivo, and reducing USP10 expression in prostate cancer cells results in elevated steady-state levels of mono-ubiquitylated H2A.Z (H2A.Zub1). Moreover, knockdown of USP10 ablates hormone-induced deubiquitylation of chromatin proteins at the AR-regulated genes. Finally, by sequential ChIP assays, we found that H2A.Zub1 is enriched at the PSA and KLK3 regulatory regions, and loss of H2A.Zub1 is associated with transcriptional activation of these genes. Together, these data provide novel insights into how H2A.Z ubiquitylation/deubiquitylation and USP10 function in AR-regulated gene expression.Keywords
This publication has 61 references indexed in Scilit:
- Characterization of the histone H2A.Z-1 and H2A.Z-2 isoforms in vertebratesBMC Biology, 2009
- Transcriptional and epigenetic functions of histone variant H2A.ZThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB’s 51st Annual Meeting – Epigenetics and Chromatin Dynamics, and has undergone the Journal’s usual peer review process.Biochemistry and Cell Biology, 2009
- Regulation of gene expression and cellular proliferation by histone H2A.ZThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB’s 51st Annual Meeting – Epigenetics and Chromatin Dynamics, and has undergone the Journal’s usual peer review process.Biochemistry and Cell Biology, 2009
- Interaction of the Glucocorticoid Receptor with the Chromatin LandscapeMolecular Cell, 2008
- A Histone H2A Deubiquitinase Complex Coordinating Histone Acetylation and H1 Dissociation in Transcriptional RegulationMolecular Cell, 2007
- Telomeric heterochromatin boundaries require NuA4-dependent acetylation of histone variant H2A.Z in SaccharomycescerevisiaeGenes & Development, 2006
- Acetylation of H2AZ Lys 14 is associated with genome-wide gene activity in yeastGenes & Development, 2006
- Variant Histone H2A.Z Is Globally Localized to the Promoters of Inactive Yeast Genes and Regulates Nucleosome PositioningPLoS Biology, 2005
- The H2A.Z/H2B dimer is unstable compared to the dimer containing the major H2A isoformProtein Science, 2005
- NUCLEASE HYPERSENSITIVE SITES IN CHROMATINAnnual Review of Biochemistry, 1988