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Aging Cell. 2017 Aug;16(4):785-796. doi: 10.1111/acel.12611. Epub 2017 May 31.

The replicative lifespan-extending deletion of SGF73 results in altered ribosomal gene expression in yeast.

Author information

1
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
2
Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
3
Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
4
Buck Institute for Research on Aging, Novato, CA, USA.
5
Department of Biochemistry, University of Washington, Seattle, WA, USA.
6
Departments of Cellular & Molecular Medicine and Neurosciences, University of California, San Diego, La Jolla, CA, USA.
7
Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
8
Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
9
Rady Children's Hospital, San Diego, CA, USA.

Abstract

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 sgf73Δ 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 sgf73Δ mutants display altered acetylation of Ifh1, an important regulator of RP gene transcription. These findings implicate altered ribosomal protein expression in sgf73Δ yeast RLS and highlight altered acetylation as a pathway of relevance for SCA7 neurodegeneration.

KEYWORDS:

Neurodegeneration; Sgf73; genome-wide occupancy; longevity gene; replicative lifespan; yeast

PMID:
28568901
PMCID:
PMC5506417
DOI:
10.1111/acel.12611
[Indexed for MEDLINE]
Free PMC Article

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