Bonizec, Melanie, Herissant, Lucas ORCID: 0000-0003-0065-5608, Pokrzywa, Wojciech ORCID: 0000-0002-5110-4462, Geng, Fuqiang, Wenzel, Sabine, Howard, Gregory C., Rodriguez, Paco, Krause, Sabine ORCID: 0000-0002-3141-886X, Tansey, William P., Hoppe, Thorsten ORCID: 0000-0002-4734-9352 and Dargemont, Catherine (2014). The ubiquitin-selective chaperone Cdc48/p97 associates with Ubx3 to modulate monoubiquitylation of histone H2B. Nucleic Acids Res., 42 (17). S. 10975 - 10987. OXFORD: OXFORD UNIV PRESS. ISSN 1362-4962

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bonizec, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herissant, LucasUNSPECIFIEDorcid.org/0000-0003-0065-5608UNSPECIFIED
Pokrzywa, WojciechUNSPECIFIEDorcid.org/0000-0002-5110-4462UNSPECIFIED
Geng, FuqiangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wenzel, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Howard, Gregory C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodriguez, PacoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krause, SabineUNSPECIFIEDorcid.org/0000-0002-3141-886XUNSPECIFIED
Tansey, William P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoppe, ThorstenUNSPECIFIEDorcid.org/0000-0002-4734-9352UNSPECIFIED
Dargemont, CatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-428382
DOI: 10.1093/nar/gku786
Journal or Publication Title: Nucleic Acids Res.
Volume: 42
Number: 17
Page Range: S. 10975 - 10987
Date: 2014
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1362-4962
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EXPORT-COMPETENT MRNP; TRANSCRIPTIONAL ACTIVATION; H3K4 TRIMETHYLATION; BUDDING YEAST; UBIQUITYLATION; PROTEIN; CHROMATIN; MONOUBIQUITINATION; DIFFERENTIATION; METHYLATIONMultiple languages
Biochemistry & Molecular BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/42838

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