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" |