Home LiteratureArticle Details
PMID: 17389396 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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 ·2007-04-03 ·Pages 5836-41

Laribee RN, Shibata Y, Mersman DP, Collins SR, Kemmeren P, Roguev A, Weissman JS, Briggs SD, Krogan NJ, Strahl BD

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.

MeSH Terms
Chromosome Mapping Chromosomes, Fungal DNA-Binding Proteins/genetics,metabolism Gene Deletion Gene Expression Regulation, Fungal Histone-Lysine N-Methyltransferase Histones/analysis,metabolism Methylation Models, Genetic Proteasome Endopeptidase Complex/genetics,metabolism Protein Structure, Tertiary Proton-Translocating ATPases/genetics,metabolism RNA, Messenger/genetics,metabolism Repressor Proteins Ribonucleases/genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Transcription Factors/genetics,metabolism Ubiquitin-Conjugating Enzymes/genetics,metabolism Ubiquitin-Protein Ligases/chemistry,genetics,metabolism
Chemicals
DNA-Binding Proteins Histones RNA, Messenger Repressor Proteins Saccharomyces cerevisiae Proteins Transcription Factors Histone-Lysine N-Methyltransferase SET1 protein, S cerevisiae Ubc4 protein, S cerevisiae Ubiquitin-Conjugating Enzymes MOT2 protein, S cerevisiae Ubiquitin-Protein Ligases CCR4 protein, S cerevisiae Ribonucleases Proteasome Endopeptidase Complex PMA1 protein, S cerevisiae Proton-Translocating ATPases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Laribee R Nicholas
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Shibata Yoichiro
Mersman Douglas P
Collins Sean R
Kemmeren Patrick
Roguev Assen
Weissman Jonathan S
Briggs Scott D
Krogan Nevan J
Strahl Brian D
References (47)
47 references, click to expand
  1. Functional organization of the yeast proteome by systematic analysis of protein complexes.
    Nature. 2002 Jan 10;415(6868):141-7 PMID: 11805826
  2. A versatile toolbox for PCR-based tagging of yeast genes: new fluorescent proteins, more markers and promoter substitution cassettes.
    Yeast. 2004 Aug;21(11):947-62 PMID: 15334558
  3. The 19S regulatory particle of the proteasome is required for efficient transcription elongation by RNA polymerase II.
    Mol Cell. 2001 May;7(5):981-91 PMID: 11389845
  4. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast.
    Nature. 2002 Jul 4;418(6893):104-8 PMID: 12077605
  5. A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling.
    Mol Cell Biol. 1999 Feb;19(2):1056-67 PMID: 9891041
  6. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.
    Cell. 2005 Nov 18;123(4):593-605 PMID: 16286008
  7. Genome-wide map of nucleosome acetylation and methylation in yeast.
    Cell. 2005 Aug 26;122(4):517-27 PMID: 16122420
  8. Do protein motifs read the histone code?
    Bioessays. 2005 Feb;27(2):164-75 PMID: 15666348
  9. Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
    Nature. 2006 Mar 30;440(7084):637-43 PMID: 16554755
  10. The yeast Ccr4-Not complex controls ubiquitination of the nascent-associated polypeptide (NAC-EGD) complex.
    J Biol Chem. 2006 Oct 20;281(42):31389-98 PMID: 16926149
  11. Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3.
    Mol Cell. 2004 Feb 13;13(3):435-42 PMID: 14967150
  12. Global loss of Set1-mediated H3 Lys4 trimethylation is associated with silencing defects in Saccharomyces cerevisiae.
    J Biol Chem. 2005 Aug 5;280(31):28761-5 PMID: 15964832
  13. Single-nucleosome mapping of histone modifications in S. cerevisiae.
    PLoS Biol. 2005 Oct;3(10):e328 PMID: 16122352
  14. Gene silencing: trans-histone regulatory pathway in chromatin.
    Nature. 2002 Aug 1;418(6897):498 PMID: 12152067
  15. Molecular regulation of histone H3 trimethylation by COMPASS and the regulation of gene expression.
    Mol Cell. 2005 Sep 16;19(6):849-56 PMID: 16168379
  16. The proteasome regulatory particle alters the SAGA coactivator to enhance its interactions with transcriptional activators.
    Cell. 2005 Nov 4;123(3):423-36 PMID: 16269334
  17. Global control of gene expression in yeast by the Ccr4-Not complex.
    Gene. 2003 Aug 14;313:1-16 PMID: 12957374
  18. The CCR4 and CAF1 proteins of the CCR4-NOT complex are physically and functionally separated from NOT2, NOT4, and NOT5.
    Mol Cell Biol. 1999 Oct;19(10):6642-51 PMID: 10490603
  19. BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex.
    Curr Biol. 2005 Aug 23;15(16):1487-93 PMID: 16040246
  20. Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by Rad6.
    J Biol Chem. 2002 Aug 9;277(32):28368-71 PMID: 12070136
  21. The language of covalent histone modifications.
    Nature. 2000 Jan 6;403(6765):41-5 PMID: 10638745
  22. Histone H2B ubiquitylation is associated with elongating RNA polymerase II.
    Mol Cell Biol. 2005 Jan;25(2):637-51 PMID: 15632065
  23. A strategy for extracting and analyzing large-scale quantitative epistatic interaction data.
    Genome Biol. 2006;7(7):R63 PMID: 16859555
  24. Global mapping of the yeast genetic interaction network.
    Science. 2004 Feb 6;303(5659):808-13 PMID: 14764870
  25. The CCR4-NOT complex plays diverse roles in mRNA metabolism.
    Prog Nucleic Acid Res Mol Biol. 2003;73:221-50 PMID: 12882519
  26. A trithorax-group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3.
    Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):90-4 PMID: 11752412
  27. Histone trimethylation by Set1 is coordinated by the RRM, autoinhibitory, and catalytic domains.
    EMBO J. 2005 Mar 23;24(6):1222-31 PMID: 15775977
  28. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter.
    Mol Cell. 2003 Jan;11(1):267-74 PMID: 12535539
  29. Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map.
    Nature. 2007 Apr 12;446(7137):806-10 PMID: 17314980
  30. Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds.
    Gene. 1995 Apr 14;156(1):119-22 PMID: 7737504
  31. The eukaryotic Ccr4-not complex: a regulatory platform integrating mRNA metabolism with cellular signaling pathways?
    Prog Nucleic Acid Res Mol Biol. 2004;77:289-322 PMID: 15196896
  32. Recruitment of a 19S proteasome subcomplex to an activated promoter.
    Science. 2002 Apr 19;296(5567):548-50 PMID: 11964484
  33. Proteome survey reveals modularity of the yeast cell machinery.
    Nature. 2006 Mar 30;440(7084):631-6 PMID: 16429126
  34. Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex.
    EMBO J. 2002 Feb 1;21(3):355-64 PMID: 11823428
  35. The Paf1 complex is essential for histone monoubiquitination by the Rad6-Bre1 complex, which signals for histone methylation by COMPASS and Dot1p.
    J Biol Chem. 2003 Sep 12;278(37):34739-42 PMID: 12876294
  36. Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena.
    Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14967-72 PMID: 10611321
  37. A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae.
    Nucleic Acids Res. 1993 Jul 11;21(14):3329-30 PMID: 8341614
  38. Active genes are tri-methylated at K4 of histone H3.
    Nature. 2002 Sep 26;419(6905):407-11 PMID: 12353038
  39. Mechanisms underlying ubiquitination.
    Annu Rev Biochem. 2001;70:503-33 PMID: 11395416
  40. Quantitative genetic analysis in Saccharomyces cerevisiae using epistatic miniarray profiles (E-MAPs) and its application to chromatin functions.
    Methods. 2006 Dec;40(4):344-52 PMID: 17101447
  41. Translating the histone code.
    Science. 2001 Aug 10;293(5532):1074-80 PMID: 11498575
  42. An epigenetic road map for histone lysine methylation.
    J Cell Sci. 2003 Jun 1;116(Pt 11):2117-24 PMID: 12730288
  43. Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae.
    Mol Cell Proteomics. 2007 Mar;6(3):439-50 PMID: 17200106
  44. Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile.
    Cell. 2005 Nov 4;123(3):507-19 PMID: 16269340
  45. Physical and functional association of RNA polymerase II and the proteasome.
    Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5904-9 PMID: 15069196
  46. The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4.
    EMBO J. 2001 Dec 17;20(24):7137-48 PMID: 11742990
  47. Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae.
    Genes Dev. 2001 Dec 15;15(24):3286-95 PMID: 11751634
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0607996104
Published
2007-04-03
Epub
2007-00-26
Pages
5836-41
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1851578
Subset
IM
Grants
NIGMS NIH HHS · R01 GM068088 · United States
NIGMS NIH HHS · R01 GM074183 · United States
NIGMS NIH HHS · GM71106-01A1 · United States
NIGMS NIH HHS · GM74183 · United States
NIGMS NIH HHS · F32 GM071106 · United States
NIGMS NIH HHS · R01 GM074183-03 · United States
NIGMS NIH HHS · GM68088 · United States
NIGMS NIH HHS · R01 GM074183-02 · United States
NIGMS NIH HHS · R01 GM074183-04 · United States
NIGMS NIH HHS · R01 GM074183-01A1 · United States
External Links
PubMed source DOI: 10.1073/pnas.0607996104 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2