title: WAC, a functional partner of RNF20/40, regulates histone H2B ubiquitination and gene transcription.
abstract: Histone H2B ubiquitination plays an important role in regulating chromatin organization during gene transcription. It has been shown that RNF20/40 regulates H2B ubiquitination. Here, using protein affinity purification, we have identified WAC as a functional partner of RNF20/40. Depletion of WAC abolishes H2B ubiquitination. WAC interacts with RNF20/40 through its C-terminal coiled-coil region and promotes RNF20/40 s E3 ligase activity for H2B ubiquitination. The N-terminal WW domain of WAC recognizes RNA polymerase II. During gene transcription, WAC targets RNF20/40 to associate with RNA polymerase II complex for H2B ubiquitination at active transcription sites, which regulates transcription. Moreover, WAC-dependent transcription is important for cell-cycle checkpoint activation in response to genotoxic stress. Taken together, our results demonstrate an important regulator for transcription-coupled histone H2B ubiquitination.
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, 1150 W. Medical Center Drive, 5560 MSRBII, Ann Arbor, MI 48109, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yu
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018816:Genes, cdc; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D006657:Histones; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D012319:RNA Polymerase II