title: Cellular aging is associated with increased ubiquitylation of histone H2B in yeast telomeric heterochromatin.
abstract: Epigenetic changes in chromatin state are associated with aging. Notably, two histone modifications have recently been implicated in lifespan regulation, namely acetylation at H4 lysine 16 in yeast and methylation at H3 lysine 4 (H3K4) in nematodes. However, less is known about other histone modifications. Here, we report that cellular aging is associated with increased ubiquitylation of histone H2B in yeast telomeric heterochromatin. An increase in ubiquitylation at histone H2B lysine 123 and methylations at both H3K4 and H3 lysine 79 (H3K79) was observed at the telomere-proximal regions of replicatively aged cells, coincident with decreased Sir2 abundance. Moreover, deficiencies in the H2B ubiquitylase complex Rad6/Bre1 as well as the deubiquitylase Ubp10 reduced the lifespan by altering both H3K4 and H3K79 methylation and Sir2 recruitment. Thus, these results show that low levels of H2B ubiquitylation are a prerequisite for a normal lifespan and the trans-tail regulation of histone modifications regulates age-associated Sir2 recruitment through telomeric silencing.
authors.affiliation: Division of Molecular and Life Sciences, College of Science and Technology, Hanyang University, Ansan, Republic of Korea.
authors.forename: Byung-Ho
authors.initials: BH
authors.lastname: Rhie
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Song
authors.forename: Hong-Yeoul
authors.initials: HY
authors.lastname: Ryu
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D016922:Cellular Senescence; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D006570:Heterochromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2
keywords: Histone ubiquitylation; Lifespan; Telomeric silencing; Trans-tail regulation