WAC, a Functional Partner of RNF20/40, Regulates Histone H2B Ubiquitination and Gene Transcription

• Published in: Molecular cell Vol. 41; no. 4; pp. 384 - 397
• Main Authors: Zhang, Feng, Yu, Xiaochun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.02.2011
• Subjects: cell cycle; Cells, Cultured; Chromatin; DNA-directed RNA polymerase; Gene Expression Regulation; gene transcription; Genes, cdc; genotoxicity; histones; Histones - genetics; Histones - metabolism; Humans; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; transcription (genetics); Transcription Initiation Site; Transcription, Genetic; Ubiquitin - genetics; Ubiquitin - metabolism; ubiquitin-protein ligase; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Ubiquitination
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2011.01.024

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. ► WAC is a binding partner of RNF20/40 ► WAC facilitates RNF20/40 and hRAD6-mediated H2B ubiquitination ► WAC associates with RNA polymerase II ► WAC functions as a linker between elongating RNA Pol II and RNF20/RNF40