Regulation of histone H3K4 tri-methylation and PAF complex recruitment by the Ccr4-Not complex.
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.
Mulder
Klaas W
KW
Department of Physiological Chemistry, University Medical Centre Utrecht, Universiteitsweg 100, Utrecht, The Netherlands.
Brenkman
Arjan B
AB
Inagaki
Akiko
A
van den Broek
Niels J F
NJ
Timmers
H Th Marc
HT
D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D009687:Nuclear Proteins / Q000378:metabolism; D012097:Repressor Proteins; D012260:Ribonucleases / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
C414164:Bur2 protein, S cerevisiae; D016213:Cyclins; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C097698:PAF1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; C086923:MOT2 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D018844:Cyclin-Dependent Kinases; C414163:SGV1 protein, S cerevisiae; D012321:DNA-Directed RNA Polymerases; C078657:CCR4 protein, S cerevisiae; D012260:Ribonucleases; D008239:Lysine