Regulation of histone H2A and H2B deubiquitination and xenopus development by USP12 and USP46

Heui Yun Joo, Amada Jones, Chunying Yang, Ling Zhai, Archer D. Smith IV, Zhuo Zhang, Mahesh B. Chandrasekharan, Zu Wen Sun, Matthew B. Renfrow, Yanming Wang, Chenbei Chang, Hengbin Wang

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)7190-7201
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number9
DOIs
StatePublished - Mar 4 2011

Fingerprint

Xenopus
Histones
Ubiquitination
Histone Code
Genes
Gastrula
Gastrulation
Chromatin Immunoprecipitation
Gene Silencing
Cell Lineage
Mesoderm
Post Translational Protein Processing
Eukaryota
Transcriptional Activation
Embryonic Structures
Gene expression
Chromatin
Staining and Labeling
Assays
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Joo, H. Y., Jones, A., Yang, C., Zhai, L., Smith IV, A. D., Zhang, Z., ... Wang, H. (2011). Regulation of histone H2A and H2B deubiquitination and xenopus development by USP12 and USP46. Journal of Biological Chemistry, 286(9), 7190-7201. https://doi.org/10.1074/jbc.M110.158311
Joo, Heui Yun ; Jones, Amada ; Yang, Chunying ; Zhai, Ling ; Smith IV, Archer D. ; Zhang, Zhuo ; Chandrasekharan, Mahesh B. ; Sun, Zu Wen ; Renfrow, Matthew B. ; Wang, Yanming ; Chang, Chenbei ; Wang, Hengbin. / Regulation of histone H2A and H2B deubiquitination and xenopus development by USP12 and USP46. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 9. pp. 7190-7201.
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Joo, HY, Jones, A, Yang, C, Zhai, L, Smith IV, AD, Zhang, Z, Chandrasekharan, MB, Sun, ZW, Renfrow, MB, Wang, Y, Chang, C & Wang, H 2011, 'Regulation of histone H2A and H2B deubiquitination and xenopus development by USP12 and USP46', Journal of Biological Chemistry, vol. 286, no. 9, pp. 7190-7201. https://doi.org/10.1074/jbc.M110.158311

Regulation of histone H2A and H2B deubiquitination and xenopus development by USP12 and USP46. / Joo, Heui Yun; Jones, Amada; Yang, Chunying; Zhai, Ling; Smith IV, Archer D.; Zhang, Zhuo; Chandrasekharan, Mahesh B.; Sun, Zu Wen; Renfrow, Matthew B.; Wang, Yanming; Chang, Chenbei; Wang, Hengbin.

In: Journal of Biological Chemistry, Vol. 286, No. 9, 04.03.2011, p. 7190-7201.

Research output: Contribution to journalArticle

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T1 - Regulation of histone H2A and H2B deubiquitination and xenopus development by USP12 and USP46

AU - Joo, Heui Yun

AU - Jones, Amada

AU - Yang, Chunying

AU - Zhai, Ling

AU - Smith IV, Archer D.

AU - Zhang, Zhuo

AU - Chandrasekharan, Mahesh B.

AU - Sun, Zu Wen

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AU - Chang, Chenbei

AU - Wang, Hengbin

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