Silent information regulator 2 (Sir2), which is the founding
member of the sirtuin family of proteins, is a pro-longevity
factor for replicative lifespan (RLS) in Saccharomyces cerevisiae.
Sir2 is required for transcriptional silencing at mating
type loci, telomeres, and rDNA loci. Sir2 also represses transcription
of highly expressed growth-related genes, such as
PMA1 and some ribosomal protein genes. Although the Sir2
paralogues Hst1, Hst2, Hst3, and Hst4 occur in S. cerevisiae,
none of them could replace the transcriptional regulation of
PMA1 by Sir2 in the wild type. In this study, we demonstrate
that Hst1, the closest Sir2 paralogue, deacetylates the acetylated
lysine 16 of histone H4 (H4K16Ac) and represses PMA1
transcription in the sir2Δ pde2Δ mutant. We further show
that Hst1 plays a role in extending the RLS of the sir2Δ pde2Δ
mutant. Collectively, our results suggest that Hst1 can substitute
for Sir2 by deacetylating H4K16Ac only in the sir2Δ
pde2Δ.
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