Role of Bmi-1 and Ring1A in H2A ubiquitylation and hox gene silencing

Ru Cao, Yu Ichi Tsukada, Yi Zhang

Research output: Contribution to journalArticle

585 Citations (Scopus)

Abstract

Polycomb group (PcG) proteins exist in at least two biochemically distinct protein complexes, the EED-EZH2 complex and the PRC1 complex, that respectively possess H3-K27 methyltransferase and H2A-K119 ubiquitin E3 ligase activities. How the enzymatic activities are regulated and what their role is in Hox gene silencing are not clear. Here, we demonstrate that Bmi-1 and Ring1A, two components of the PRC1 complex, play important roles in H2A ubiquitylation and Hox gene silencing. We show that both proteins positively regulate H2A ubiquitylation. Chromatin immunoprecipitation (ChIP) assays demonstrate that Bmi-1 and other components of the two PcG complexes bind to the promoter of HoxC13. Knockout Bmi-1 results in significant loss of H2A ubiquitylation and upregulation of Hoxc13 expression, whereas EZH2-mediated H3-K27 methylation is not affected. Our results suggest that EZH2-mediated H3-K27 methylation functions upstream of PRC1 and establishes a critical role for Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing.

Original languageEnglish
Pages (from-to)845-854
Number of pages10
JournalMolecular Cell
Volume20
Issue number6
DOIs
Publication statusPublished - Dec 22 2005
Externally publishedYes

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Homeobox Genes
Ubiquitination
Gene Silencing
Methylation
Polycomb-Group Proteins
Ubiquitin-Protein Ligases
Chromatin Immunoprecipitation
Methyltransferases
Proteins
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Role of Bmi-1 and Ring1A in H2A ubiquitylation and hox gene silencing. / Cao, Ru; Tsukada, Yu Ichi; Zhang, Yi.

In: Molecular Cell, Vol. 20, No. 6, 22.12.2005, p. 845-854.

Research output: Contribution to journalArticle

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