CCR4/NOT complex associates with the proteasome and regulates histone methylation

R. Nicholas Laribee, Yoichiro Shibata, Douglas P. Mersman, Sean R. Collins, Patrick Kemmeren, Assen Roguev, Jonathan S. Weissman, Scott D. Briggs, Nevan J. Krogan, Brian D. Strahl

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The proteasome regulates histone lysine methylation and gene transcription, but how it does so is poorly understood. To better understand this process, we used the epistatic miniarray profile (E-MAP) approach to identify factors that genetically interact with proteasomal subunits. In addition to members of the Set1 complex that mediate histone H3 lysine 4 methylation (H3K4me), we found that deleting members of the CCR4/NOT mRNA processing complex exhibit synthetic phenotypes when combined with proteasome mutants. Further biochemical analyses revealed physical associations between CCR4/NOT and the proteasome in vivo. Consistent with the genetic and biochemical interactions linking CCR4/NOT with proteasome and Set1-mediated methylation, we find that loss of Not4 decreases global and gene-specific H3K4 trimethylation (H3K4me3) and decreases 19S proteasome recruitment to the PMA1 gene. Similar to proteasome regulation of histone methylation, loss of CCR4/NOT members does not affect ubiquitinated H2B. Mapping of Not4 identified the RING finger domain as essential for H3K4me3, suggesting a role for ubiquitin in this process. Consistent with this idea, loss of the Not4-interacting protein Ubc4, a known ubiquitin-conjugating enzyme, decreases H3K4me3. These studies implicate CCR4/NOT in the regulation of H3K4me3 through a ubiquitin-dependent pathway that likely involves the proteasome.

Original languageEnglish (US)
Pages (from-to)5836-5841
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number14
DOIs
StatePublished - Apr 3 2007

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Proteasome Endopeptidase Complex
Histones
Methylation
Ubiquitin
Lysine
RING Finger Domains
Ubiquitin-Conjugating Enzymes
Genes
Molecular Biology
Phenotype
Messenger RNA
Proteins

Keywords

  • 19S proteasome
  • COMPASS
  • Transcription

ASJC Scopus subject areas

  • General

Cite this

CCR4/NOT complex associates with the proteasome and regulates histone methylation. / Laribee, R. Nicholas; Shibata, Yoichiro; Mersman, Douglas P.; Collins, Sean R.; Kemmeren, Patrick; Roguev, Assen; Weissman, Jonathan S.; Briggs, Scott D.; Krogan, Nevan J.; Strahl, Brian D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 14, 03.04.2007, p. 5836-5841.

Research output: Contribution to journalArticle

Laribee, RN, Shibata, Y, Mersman, DP, Collins, SR, Kemmeren, P, Roguev, A, Weissman, JS, Briggs, SD, Krogan, NJ & Strahl, BD 2007, 'CCR4/NOT complex associates with the proteasome and regulates histone methylation', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 14, pp. 5836-5841. https://doi.org/10.1073/pnas.0607996104
Laribee, R. Nicholas ; Shibata, Yoichiro ; Mersman, Douglas P. ; Collins, Sean R. ; Kemmeren, Patrick ; Roguev, Assen ; Weissman, Jonathan S. ; Briggs, Scott D. ; Krogan, Nevan J. ; Strahl, Brian D. / CCR4/NOT complex associates with the proteasome and regulates histone methylation. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 14. pp. 5836-5841.
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