title: Dot1 and histone H3K79 methylation in natural telomeric and HM silencing.
abstract: The expression of genes residing near telomeres is attenuated through telomere position-effect variegation (TPEV). By using a URA3 reporter located at TEL-VII-L of Saccharomyces cerevisiae, it was proposed that the disruptor of telomeric silencing-1 (Dot1) regulates TPEV by catalyzing H3K79 methylation. URA3 reporter assays also indicated that H3K79 methylation is required for HM silencing. Surprisingly, a genome-wide expression analysis of H3K79 methylation-defective mutants identified only a few telomeric genes, such as COS12 at TEL-VII-L, to be subject to H3K79 methylation-dependent natural silencing. Consistently, loss of Dot1 did not globally alter Sir2 or Sir3 occupancy in subtelomeric regions, but only led to some telomere-specific changes. Furthermore, H3K79 methylation by Dot1 did not play a role in the maintenance of natural HML silencing. Therefore, commonly used URA3 reporter assays may not report on natural PEV, and therefore, studies concerning the epigenetic mechanism of silencing in yeast should also employ assays reporting on natural gene expression patterns.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Yoh-Hei
authors.initials: YH
authors.lastname: Takahashi
authors.forename: Julia M
authors.initials: JM
authors.lastname: Schulze
authors.forename: Jessica
authors.initials: J
authors.lastname: Jackson
authors.forename: Thomas
authors.initials: T
authors.lastname: Hentrich
authors.forename: Chris
authors.initials: C
authors.lastname: Seidel
authors.forename: Sue L
authors.initials: SL
authors.lastname: Jaspersen
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kobor
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D055012:Chromosomal Position Effects; D020868:Gene Silencing; D005800:Genes, Fungal; D055106:Genome-Wide Association Study; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D063209:N-Terminal Acetyltransferase A; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2 / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D009687:Nuclear Proteins; C084122:SIR3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; D000123:Acetyltransferases; D063209:N-Terminal Acetyltransferase A; C540858:ARD1 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2