The ubiquitin-selective chaperone Cdc48/p97 associates with Ubx3 to modulate monoubiquitylation of histone H2B

• Published in: Nucleic acids research Vol. 42; no. 17; pp. 10975 - 10986
• Main Authors: Bonizec, Mélanie, Hérissant, Lucas, Pokrzywa, Wojciech, Geng, Fuqiang, Wenzel, Sabine, Howard, Gregory C, Rodriguez, Paco, Krause, Sabine, Tansey, William P, Hoppe, Thorsten, Dargemont, Catherine
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 29.09.2014
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Biochemistry, Molecular Biology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line; Cells, Cultured; Female; Gene regulation, Chromatin and Epigenetics; Histones - metabolism; Humans; Life Sciences; Male; Molecular Chaperones - metabolism; Mutation; Myoblasts - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Ubiquitination; Valosin Containing Protein
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gku786

Cdc48/p97 is an evolutionary conserved ubiquitin-dependent chaperone involved in a broad array of cellular functions due to its ability to associate with multiple cofactors. Aside from its role in removing RNA polymerase II from chromatin after DNA damage, little is known about how this AAA-ATPase is involved in the transcriptional process. Here, we show that yeast Cdc48 is recruited to chromatin in a transcription-coupled manner and modulates gene expression. Cdc48, together with its cofactor Ubx3 controls monoubiquitylation of histone H2B, a conserved modification regulating nucleosome dynamics and chromatin organization. Mechanistically, Cdc48 facilitates the recruitment of Lge1, a cofactor of the H2B ubiquitin ligase Bre1. The function of Cdc48 in controlling H2B ubiquitylation appears conserved in human cells because disease-related mutations or chemical inhibition of p97 function affected the amount of ubiquitylated H2B in muscle cells. Together, these results suggest a prominent role of Cdc48/p97 in the coordination of chromatin remodeling with gene transcription to define cellular differentiation processes.