期刊
AGING CELL
卷 16, 期 4, 页码 785-796出版社
WILEY
DOI: 10.1111/acel.12611
关键词
genome-wide occupancy; longevity gene; Neurodegeneration; replicative lifespan; Sgf73; yeast
资金
- NIH [R01 EY014061, R01 AG033082, R01 GM090177, T32 GM008666, T32 AG000266, F32 GM089101]
Sgf73, a core component of SAGA, is the yeast orthologue of ataxin-7, which undergoes CAG-polyglutamine repeat expansion. leading to the human neurodegenerative disease spinocerebellar ataxia type 7 (SCA7). Deletion of SGF73 dramatically extends replicative lifespan (RLS) in yeast. To further define the basis for Sgf73-mediated RLS extension, we performed ChIP-Seq, identified 388 unique genomic regions occupied by Sgf73, and noted enrichment in promoters of ribosomal protein (RP)-encoding genes. Of 388 Sgf73 binding sites, 33 correspond to 5 regions of genes implicated in RLS extension, including 20 genes encoding RPs. Furthermore, half of Sgf73-occupied, RLS-linked RP genes displayed significantly reduced expression in sgf73 Delta mutants, and double null strains lacking SGF73 and a Sgf73-regulated, RLS linked RP gene exhibited no further increase in replicative lifespan. We also found that sgf73 Delta mutants display altered acetylation of lfhl, an important regulator of RP gene transcription. These findings implicate altered ribosomal protein expression in sgf73 Delta yeast RLS and highlight altered acetylation as a pathway of relevance for SCA7 neurodegeneration.
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