title: Effectors of lysine 4 methylation of histone H3 in Saccharomyces cerevisiae are negative regulators of PHO5 and GAL1-10.
abstract: Post-translational modifications of histone amino-terminal tails are a key determinant in gene expression. Histone methylation plays a dual role in gene regulation. Methylation of lysine 9 of histone H3 in higher eukaryotes is associated with transcriptionally inactive heterochromatin, whereas H3 lysine 4 methylation correlates with active chromatin. Methylation of lysine 4 of H3 via Set1, a component of the Saccharomyces cerevisiae COMPASS complex, is regulated by the transcriptional elongation Paf1-Rtf1 and histone ubiquitination Rad6-Bre1 complexes, which are required for the expression of a subset of genes. This suggests that lysine 4 methylation of histone H3 may play an activating role in transcription; however, the mechanism of Set1 function remains unclear. We show here that H3 lysine 4 methylation also negatively regulated gene expression, as strains without Set1 showed enhanced expression of PHO5, wherein chromatin structure plays an important transcriptional regulatory role. Di- and trimethylation of H3 lysine 4 was detected at the PHO5 promoter, and a strain expressing a mutant version of histone H3 with lysine 4 changed to arginine, (which cannot be methylated) exhibited PHO5 derepression. Moreover, PHO5 was derepressed in strains that lacked components of either the Paf1-Rtf1 elongation or Rad6-Bre1 histone ubiquitination complexes. Lastly, PHO84 and GAL1-10 transcription was also increased in set1Delta cells. These results suggest that H3 methylation at lysine 4, in conjunction with transcriptional elongation, may function in a negative feedback pathway for basal transcription of some genes, although being a positive effector at others.
authors.affiliation: Department of Biochemistry & Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Carvin
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kladde
mesh_terms: D000135:Acid Phosphatase; D002352:Carrier Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D025461:Feedback, Physiological; D017353:Gene Deletion; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000502:physiology; D016133:Polymerase Chain Reaction; D028081:Proton-Phosphate Symporters / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D035181:TATA-Box Binding Protein / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000502:physiology
chemical_list: C472168:Bre1 protein, S cerevisiae; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C097698:PAF1 protein, S cerevisiae; C105495:PHO84 protein, S cerevisiae; D028081:Proton-Phosphate Symporters; D012333:RNA, Messenger; C107273:RTF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D025801:Ubiquitin; C026989:thiamine-binding protein; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D000135:Acid Phosphatase; C488913:PHO3 protein, S cerevisiae; C488916:PHO5 protein, S cerevisiae; D008239:Lysine