Effectors of Lysine 4 Methylation of Histone H3 in Saccharomyces cerevisiae Are Negative Regulators of PHO5 and GAL1-10

• Published in: The Journal of biological chemistry 2004-08, Vol.279 (32), p.33057-33062
• Main Authors: Carvin, Christopher D., Kladde, Michael P.
• Format: Article
• Language: English
• Subjects: 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; 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
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M405033200

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 set1Δ 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.