Monoubiquitination of human histone H2B: The factors involved and their roles in HOX gene regulation Journal Article


Authors: Zhu, B.; Zheng, Y.; Pham, A. D.; Mandal, S. S.; Erdjument-Bromage, H.; Tempst, P.; Reinberg, D.
Article Title: Monoubiquitination of human histone H2B: The factors involved and their roles in HOX gene regulation
Abstract: 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. Copyright ©2005 by Elsevier Inc.
Keywords: controlled study; protein expression; unclassified drug; human cell; ubiquitin; mammalia; complex formation; gene overexpression; small interfering rna; rna interference; genetic transcription; homeodomain proteins; in vitro study; hela cells; dna methylation; nuclear proteins; gene expression regulation; gene activation; ubiquitination; hybrid protein; histone h3; gene control; yeast; sequence homology; ubiquitin-conjugating enzymes; histone h2b; ubiquitin-protein ligases; rna polymerase ii; histones; isoprotein; lysine; ligase; ubiquitin conjugating enzyme; isoenzyme; hox gene; protein bre1; protein ubch6
Journal Title: Molecular Cell
Volume: 20
Issue: 4
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2005-11-23
Start Page: 601
End Page: 611
Language: English
DOI: 10.1016/j.molcel.2005.09.025
PUBMED: 16307923
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 161" - "Export Date: 24 October 2012" - "CODEN: MOCEF" - "Source: Scopus"
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  1. Paul J Tempst
    324 Tempst