Effectors of lysine 4 methylation of histone H3 in Saccharomyces cerevisiae are negative regulators of PHO5 and GAL1-10

J Biol Chem. 2004 Aug 6;279(32):33057-62. doi: 10.1074/jbc.M405033200. Epub 2004 Jun 4.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acid Phosphatase
  • Carrier Proteins / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Feedback, Physiological
  • Gene Deletion
  • Gene Expression Regulation*
  • Histone-Lysine N-Methyltransferase
  • Histones / chemistry
  • Histones / metabolism*
  • Lysine / metabolism*
  • Methylation
  • Mutagenesis
  • Nuclear Proteins / physiology
  • Polymerase Chain Reaction
  • Proton-Phosphate Symporters / genetics
  • RNA, Messenger / analysis
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology
  • TATA-Box Binding Protein / physiology
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Transcription, Genetic
  • Ubiquitin / metabolism
  • Ubiquitin-Conjugating Enzymes / physiology

Substances

  • Bre1 protein, S cerevisiae
  • Carrier Proteins
  • DNA-Binding Proteins
  • Histones
  • Nuclear Proteins
  • PAF1 protein, S cerevisiae
  • PHO84 protein, S cerevisiae
  • Proton-Phosphate Symporters
  • RNA, Messenger
  • RTF1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • TATA-Box Binding Protein
  • Transcription Factors
  • Ubiquitin
  • thiamine-binding protein
  • Histone-Lysine N-Methyltransferase
  • SET1 protein, S cerevisiae
  • RAD6 protein, S cerevisiae
  • Ubiquitin-Conjugating Enzymes
  • Acid Phosphatase
  • PHO3 protein, S cerevisiae
  • PHO5 protein, S cerevisiae
  • Lysine