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Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation.

Molecular cell | Nov 23, 2005

http://www.ncbi.nlm.nih.gov/pubmed/16307923

In yeast, histone H2B monoubiquitination is a cotranscriptional event regulating histone H3 methylation at lysines 4 and 79. However, mammalian H2B monoubiquitination remains poorly understood. We report that in humans, the 600 kDa RNF20/40 complex is the E3 ligase and UbcH6 is the ubiquitin E2-conjugating enzyme for H2B-Lys120 monoubiquitination. RNF20 and RNF40 are both homologs of Bre1, the E3 ligase in the yeast case. UbcH6 physically interacts with RNF20/40 and with the hPAF complex. Formation of a trimeric complex with hPAF stimulates H2B monoubiquitination activity in vitro. Accordingly, UbcH6, RNF20/40, and the hPAF complex are recruited to transcriptionally active genes in vivo. RNF20 overexpression leads to elevated H2B monoubiquitination, subsequently higher levels of methylation at H3 lysines 4 and 79, and stimulation of HOX gene expression. In contrast, RNAi against the RNF20/40 complex or hPAF complex reduces H2B monoubiquitination, lowers methylation levels at H3 lysines 4 and 79, and represses HOX gene expression.

Pubmed ID: 16307923 RIS Download

Mesh terms: DNA Methylation | Gene Expression Regulation | HeLa Cells | Histones | Homeodomain Proteins | Humans | Nuclear Proteins | RNA Interference | RNA Polymerase II | Ubiquitin | Ubiquitin-Conjugating Enzymes | Ubiquitin-Protein Ligases

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM37120
  • Agency: NCI NIH HHS, Id: P30 CA08748

BioGRID (Data, Interactions)

GO (Data, Gene Annotation)

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