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PMID: 17392337 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of histone H3K4 tri-methylation and PAF complex recruitment by the Ccr4-Not complex.

Nucleic acids research ·Vol. 35 ·No. 7 ·2007-00-00 ·Pages 2428-39

Mulder KW, Brenkman AB, Inagaki A, van den Broek NJ, Timmers HT

Abstract

Efficient transcription is linked to modification of chromatin. For instance, tri-methylation of lysine 4 on histone H3 (H3K4) strongly correlates with transcriptional activity and is regulated by the Bur1/2 kinase complex. We found that the evolutionarily conserved Ccr4-Not complex is involved in establishing H3K4 tri-methylation in Saccharomyces cerevisiae. We observed synthetic lethal interactions of Ccr4-Not components with BUR1 and BUR2. Further analysis indicated that the genes encoding the Not-proteins are essential for efficient regulation of H3K4me3, but not H3K4me1/2, H3K36me2 or H3K79me2/3 levels. Moreover, regulation of H3K4me3 levels by NOT4 is independent of defects in RNA polymerase II loading. We found NOT4 to be important for ubiquitylation of histone H2B via recruitment of the PAF complex, but not for recruitment or activation of the Bur1/2 complex. These results suggest a mechanism in which the Ccr4-Not complex functions parallel to or downstream of the Bur1/2 kinase to facilitate H3K4me3 via PAF complex recruitment.

MeSH Terms
Cyclin-Dependent Kinases/genetics,metabolism Cyclins/genetics,metabolism DNA-Binding Proteins/metabolism DNA-Directed RNA Polymerases/metabolism Gene Deletion Gene Expression Regulation, Fungal Histone-Lysine N-Methyltransferase/metabolism Histones/chemistry,metabolism Lysine/metabolism Methylation Nuclear Proteins/metabolism Repressor Proteins Ribonucleases/genetics,physiology Saccharomyces cerevisiae/enzymology,genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism,physiology Transcription Factors/metabolism Ubiquitin/metabolism Ubiquitin-Protein Ligases/genetics,physiology
Chemicals
Bur2 protein, S cerevisiae Cyclins DNA-Binding Proteins Histones Nuclear Proteins PAF1 protein, S cerevisiae Repressor Proteins Saccharomyces cerevisiae Proteins Transcription Factors Ubiquitin Histone-Lysine N-Methyltransferase SET1 protein, S cerevisiae MOT2 protein, S cerevisiae Ubiquitin-Protein Ligases Cyclin-Dependent Kinases SGV1 protein, S cerevisiae DNA-Directed RNA Polymerases CCR4 protein, S cerevisiae Ribonucleases Lysine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mulder Klaas W
Department of Physiological Chemistry, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht, The Netherlands.
Brenkman Arjan B
Inagaki Akiko
van den Broek Niels J F
Timmers H Th Marc
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkm175
Published
2007-00-00
Epub
2007-00-28
Pages
2428-39
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1874646
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkm175 PMC Full Text View journal details
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