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Dot1 and Histone H3K79 Methylation in Natural Heterochromatic and HML/HMR Silencing

ABSTRACT: Dot1 is a methyl transferase that has been shown through a reporter gene to be involved in position effect variegation of gene expression in heterochrmatic regions such as telomeres and the mating type loci in yeast. This study examines the effect of mutation of DOT1 and two other proteins involved in H3K79 methylation, SWI4 and ARD1, on gene expression relative to wt cells. Wt, and mutants of Dot1, Swi4, or Ard1 were grown, in duplicate, in liquid media to midlog phase for extraction of RNA and comparison of gene expression on Affymetrix arrays.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Chris Seidel

PROVIDER: E-GEOD-27234 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Dot1 and histone H3K79 methylation in natural telomeric and HM silencing.

Takahashi Yoh-Hei YH Schulze Julia M JM Jackson Jessica J Hentrich Thomas T Seidel Chris C Jaspersen Sue L SL Kobor Michael S MS Shilatifard Ali A

Molecular cell 20110401 1

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 f ...[more]

PMID: 21474073

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Dot1 and Histone H3K79 Methylation in Natural Heterochromatic and HML/HMR Silencing

Project description:Dot1 is a methyl transferase that has been shown through a reporter gene to be involved in position effect variegation of gene expression in heterochrmatic regions such as telomeres and the mating type loci in yeast. This study examines the effect of mutation of DOT1 and two other proteins involved in H3K79 methylation, SWI4 and ARD1, on gene expression relative to wt cells.

2011-02-12 | GSE27234 | GEO

Dot1 and Histone H3K79 Methylation in Natural Heterochromatic and HML-HMR Silencing

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2011-02-09 | E-MEXP-3108 | biostudies-arrayexpress

Chromatin immunoprecipitation in dot1 deletion and G1 or G2 arrested yeast cells to identify methylation patterns

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Project description:The glycolytic enzyme, pyruvate kinase Pyk1 maintains telomere heterochromatin by phosphorylating histone H3T11 (H3pT11), which promotes SIR (silent information regulator) complex binding at telomeres and prevents autophagy-mediated Sir2 degradation. However, the exact action mechanism of H3pT11 is poorly understood. Here, we report that H3pT11 directly inhibits Dot1-catalyzed H3K79 tri-methylation (H3K79me3) and uncover how this histone crosstalk regulates autophagy and telomere silencing. Mechanistically, Pyk1-catalyzed H3pT11 directly reduces the binding of Dot1 to chromatin and inhibits Dot1-catalyzed H3K79me3, which leads to transcriptional repression of autophagy genes and reduced autophagy. Despite the antagonism between H3pT11 and H3K79me3, they work together to promote the binding of SIR complex at telomeres to maintain telomere silencing. Furthermore, we identify Reb1 as a telomere-associated factor that recruits Pyk1-containing SESAME (Serine-responsive SAM36 taining Metabolic Enzyme) complex to telomere regions to phosphorylate H3T11 and prevent the invasion of H3K79me3 from euchromatin into heterochromatin to maintain telomere silencing. Together, these results uncover a novel histone crosstalk and provide insights into dynamic regulation of silent heterochromatin and autophagy in response to cell metabolism.

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DOT-1.1 (DOT1L) deficiency in C. elegans leads to small RNA-dependent gene activation [small RNA, L3]

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