Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2011 Mar 04;2869:7190-201. doi: 10.1074/jbc.M110.158311.
Show Gene links
Show Anatomy links
Regulation of histone H2A and H2B deubiquitination and Xenopus development by USP12 and USP46.
Joo HY
,
Jones A
,
Yang C
,
Zhai L
,
Smith AD
,
Zhang Z
,
Chandrasekharan MB
,
Sun ZW
,
Renfrow MB
,
Wang Y
,
Chang C
,
Wang H
.
???displayArticle.abstract???
Post-translational histone modifications play important roles in regulating gene expression programs, which in turn determine cell fate and lineage commitment during development. One such modification is histone ubiquitination, which primarily targets histone H2A and H2B. Although ubiquitination of H2A and H2B has been generally linked to gene silencing and gene activation, respectively, the functions of histone ubiquitination during eukaryote development are not well understood. Here, we identified USP12 and USP46 as histone H2A and H2B deubiquitinases that regulate Xenopus development. USP12 and USP46 prefer nucleosomal substrates and deubiquitinate both histone H2A and H2B in vitro and in vivo. WDR48, a WD40 repeat-containing protein, interacts with USP12 and USP46 and is required for the histone deubiquitination activity. Overexpression of either gene leads to gastrulation defects without affecting mesodermal cell fate, whereas knockdown of USP12 in Xenopus embryos results in reduction of a subset of mesodermal genes at gastrula stages. Immunohistochemical staining and chromatin immunoprecipitation assays revealed that USP12 regulates histone deubiquitination in the mesoderm and at specific gene promoters during Xenopus development. Taken together, this study identifies USP12 and USP46 as histone deubiquitinases for H2A and H2B and reveals that USP12 regulates Xenopus development during gastrula stages.
Blythe,
Chromatin immunoprecipitation in early Xenopus laevis embryos.
2009, Pubmed,
Xenbase
Blythe,
Chromatin immunoprecipitation in early Xenopus laevis embryos.
2009,
Pubmed
,
Xenbase
Brognard,
PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms.
2007,
Pubmed
Campos,
Histones: annotating chromatin.
2009,
Pubmed
Chandrasekharan,
Histone H2B C-terminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination.
2010,
Pubmed
Chang,
A Xenopus type I activin receptor mediates mesodermal but not neural specification during embryogenesis.
1997,
Pubmed
,
Xenbase
Clauser,
Role of accurate mass measurement (+/- 10 ppm) in protein identification strategies employing MS or MS/MS and database searching.
1999,
Pubmed
Cohn,
UAF1 is a subunit of multiple deubiquitinating enzyme complexes.
2009,
Pubmed
Cohn,
A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway.
2007,
Pubmed
Daniel,
Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription.
2004,
Pubmed
Dignam,
Eukaryotic gene transcription with purified components.
1983,
Pubmed
,
Xenbase
Emre,
Maintenance of low histone ubiquitylation by Ubp10 correlates with telomere-proximal Sir2 association and gene silencing.
2005,
Pubmed
Eng,
An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.
1994,
Pubmed
Espinosa,
Histone H2B ubiquitination: the cancer connection.
2008,
Pubmed
Gardner,
Ubp10/Dot4p regulates the persistence of ubiquitinated histone H2B: distinct roles in telomeric silencing and general chromatin.
2005,
Pubmed
Henry,
Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8.
2003,
Pubmed
Hirst,
Epigenetics and human disease.
2009,
Pubmed
Hwang,
A conserved RING finger protein required for histone H2B monoubiquitination and cell size control.
2003,
Pubmed
Jason,
Histone ubiquitination: a tagging tail unfolds?
2002,
Pubmed
Jones,
The epigenomics of cancer.
2007,
Pubmed
Joo,
Regulation of cell cycle progression and gene expression by H2A deubiquitination.
2007,
Pubmed
,
Xenbase
Kee,
WDR20 regulates activity of the USP12 x UAF1 deubiquitinating enzyme complex.
2010,
Pubmed
Keller,
Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search.
2002,
Pubmed
Kim,
The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions.
2005,
Pubmed
Kim,
RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells.
2009,
Pubmed
Ko,
Chromatin remodeling, development and disease.
2008,
Pubmed
Kouzarides,
Chromatin modifications and their function.
2007,
Pubmed
Li,
Regulation of p53 target gene expression by peptidylarginine deiminase 4.
2008,
Pubmed
Li,
The role of chromatin during transcription.
2007,
Pubmed
Martin,
The diverse functions of histone lysine methylation.
2005,
Pubmed
Mohn,
Genetics and epigenetics: stability and plasticity during cellular differentiation.
2009,
Pubmed
Nakagawa,
Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation.
2008,
Pubmed
Nesvizhskii,
A statistical model for identifying proteins by tandem mass spectrometry.
2003,
Pubmed
Nicassio,
Human USP3 is a chromatin modifier required for S phase progression and genome stability.
2007,
Pubmed
Orlando,
Polycomb, epigenomes, and control of cell identity.
2003,
Pubmed
Osley,
Regulation of histone H2A and H2B ubiquitylation.
2006,
Pubmed
Perkins,
Probability-based protein identification by searching sequence databases using mass spectrometry data.
1999,
Pubmed
Renfrow,
Analysis of O-glycan heterogeneity in IgA1 myeloma proteins by Fourier transform ion cyclotron resonance mass spectrometry: implications for IgA nephropathy.
2007,
Pubmed
Reyes-Turcu,
Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes.
2009,
Pubmed
Robzyk,
Rad6-dependent ubiquitination of histone H2B in yeast.
2000,
Pubmed
Scheuermann,
Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB.
2010,
Pubmed
Shanbhag,
ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks.
2010,
Pubmed
Sowa,
Defining the human deubiquitinating enzyme interaction landscape.
2009,
Pubmed
Sun,
Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast.
2002,
Pubmed
Wang,
Role of histone H2A ubiquitination in Polycomb silencing.
2004,
Pubmed
Wang,
Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein.
2009,
Pubmed
Weake,
Histone ubiquitination: triggering gene activity.
2008,
Pubmed
Weake,
SAGA-mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system.
2008,
Pubmed
Wood,
Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter.
2003,
Pubmed
Zhang,
The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression.
2008,
Pubmed
Zhang,
USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A.
2008,
Pubmed
Zhao,
A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing.
2008,
Pubmed
Zhu,
A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation.
2007,
Pubmed
Zhu,
Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation.
2005,
Pubmed
de Napoles,
Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation.
2004,
Pubmed
van der Knaap,
GMP synthetase stimulates histone H2B deubiquitylation by the epigenetic silencer USP7.
2005,
Pubmed
