Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation.
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.
Zhu
Bing
B
Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 683 Hoes Lane, Piscataway, New Jersey 08854, USA.
Zheng
Yong
Y
Pham
Anh-Dung
AD
Mandal
Subhrangsu S
SS
Erdjument-Bromage
Hediye
H
Tempst
Paul
P
Reinberg
Danny
D
D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012319:RNA Polymerase II / Q000502:physiology; D014157:Transcription Factors; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
D006657:Histones; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C501972:PAF1 protein, human; D014157:Transcription Factors; D025801:Ubiquitin; C489963:UBE2E1 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C506646:RNF20 protein, human; C413363:RNF40 protein, human; D044767:Ubiquitin-Protein Ligases; D012319:RNA Polymerase II