Kang Woo Kyu, Devare Mayur, Kim Jeong-Yoon
Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, 34134, Republic of Korea.
Department of Neurobiology, University of Massachusetts Medical School, Worcester, USA.
J Microbiol. 2017 Feb;55(2):123-129. doi: 10.1007/s12275-017-6535-z. Epub 2017 Jan 26.
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.
沉默信息调节因子2（Sir2）是sirtuin蛋白家族的创始成员，是酿酒酵母复制寿命（RLS）的长寿因子。Sir2是交配型位点、端粒和rDNA位点转录沉默所必需的。Sir2还抑制高表达的生长相关基因的转录，如PMA1和一些核糖体蛋白基因。虽然Sir2旁系同源物Hst1、Hst2、Hst3和Hst4存在于酿酒酵母中，但在野生型中它们都不能替代Sir2对PMA1的转录调控。在本研究中，我们证明，与Sir2最接近的旁系同源物Hst1可使组蛋白H4的乙酰化赖氨酸16（H4K16Ac）去乙酰化，并在sir2Δ pde2Δ突变体中抑制PMA1转录。我们进一步表明，Hst1在延长sir2Δ pde2Δ突变体的RLS中发挥作用。总的来说，我们的结果表明，Hst1仅在sir2Δ pde2Δ中通过使H4K16Ac去乙酰化来替代Sir2。
