title: The ubiquitin-selective chaperone Cdc48/p97 associates with Ubx3 to modulate monoubiquitylation of histone H2B.
abstract: 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.
authors.affiliation: Sorbonne Paris Cité, INSERM UMR944, CNRS UMR7212, Equipe labellisée Ligue contre le cancer, University of Paris Diderot, Hôpital St. Louis 1, Avenue Claude Vellefaux 75475 Paris Cedex 10, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Bonizec
authors.affiliation: Sorbonne Paris Cité, INSERM UMR944, CNRS UMR7212, Equipe labellisée Ligue contre le cancer, University of Paris Diderot, Hôpital St. Louis 1, Avenue Claude Vellefaux 75475 Paris Cedex 10, France.
authors.forename: Lucas
authors.initials: L
authors.lastname: Hérissant
authors.affiliation: Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Pokrzywa
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 465 21st Avenue South, Nashville, TN 37232, USA.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Geng
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 465 21st Avenue South, Nashville, TN 37232, USA.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wenzel
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 465 21st Avenue South, Nashville, TN 37232, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Howard
authors.affiliation: Sorbonne Paris Cité, INSERM UMR944, CNRS UMR7212, Equipe labellisée Ligue contre le cancer, University of Paris Diderot, Hôpital St. Louis 1, Avenue Claude Vellefaux 75475 Paris Cedex 10, France.
authors.forename: Paco
authors.initials: P
authors.lastname: Rodriguez
authors.affiliation: Laboratory for Molecular Myology, Friedrich Baur Institute, Department of Neurology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Krause
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, 465 21st Avenue South, Nashville, TN 37232, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Tansey
authors.affiliation: Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hoppe
authors.affiliation: Sorbonne Paris Cité, INSERM UMR944, CNRS UMR7212, Equipe labellisée Ligue contre le cancer, University of Paris Diderot, Hôpital St. Louis 1, Avenue Claude Vellefaux 75475 Paris Cedex 10, France catherine.dargemont@inserm.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dargemont
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism*; D009154:Mutation; D032446:Myoblasts / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D054875:Ubiquitination; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; C497163:Lge1 protein, S cerevisiae; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C000595516:Ubx3 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C000614177:CDC48 protein, S cerevisiae; D000074405:Valosin Containing Protein