title: Global loss of Set1-mediated H3 Lys4 trimethylation is associated with silencing defects in Saccharomyces cerevisiae.
abstract: Post-translational histone modifications, such as acetylation, phosphorylation, ubiquitination, and methylation, have been correlated with regulation of gene expression. In Saccharomyces cerevisiae, Set1 has been identified as the sole histone methyltransferase required for histone H3 lysine 4 (Lys(4)) methylation. Yeast cells that do not express Set1 have several apparent phenotypes, including slow growth and defects in telomere, HML, and rDNA silencing. However, the mechanism by which the Set1 methyltransferase mediates differential histone H3 methylation (mono-, di-, and tri-) is still not understood, and the involvement of domains or regions in Set1 contributing to H3 Lys(4) methylation has not been well characterized. In this study, the N terminus of Set1 was shown to be important for global and gene specific histone H3 trimethylation. We show that Set1 trimethyl-defective mutants can rescue a set1Delta slow growth defect. In contrast, Set1 trimethyl mutants were defective in telomere, rDNA, HML, and HMR silencing. Taken together, these data suggest that histone H3 Lys(4) trimethylation is required for proper silencing, while mono- and/or dimethylation is sufficient for cell growth.
authors.affiliation: Department of Biochemistry and the Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Fingerman
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Wu
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Wilson
authors.forename: Scott D
authors.initials: SD
authors.lastname: Briggs
mesh_terms: D001483:Base Sequence; D002455:Cell Division; D017931:DNA Primers; D004271:DNA, Fungal / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D010446:Peptide Fragments / Q000378:metabolism; D010957:Plasmids; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D004271:DNA, Fungal; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D008239:Lysine