Functional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.

Sirtuins, class III histone deacetylases, are proteins homologous to the yeast protein Sir2p. Mammalian Sirt1 has been shown to be involved in energy metabolism, brain functions, inflammation and aging through its deacetylase activity, acting on both histone and non-histone substrates. In order to v...

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Autores principales:	Davide Gaglio, Anna D'Alfonso, Giorgio Camilloni
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9fcdef6a744448c1a7f0cabdb63ce364
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spelling	oai:doaj.org-article:9fcdef6a744448c1a7f0cabdb63ce3642021-11-18T08:42:21ZFunctional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.1932-620310.1371/journal.pone.0083114https://doaj.org/article/9fcdef6a744448c1a7f0cabdb63ce3642013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349441/?tool=EBIhttps://doaj.org/toc/1932-6203Sirtuins, class III histone deacetylases, are proteins homologous to the yeast protein Sir2p. Mammalian Sirt1 has been shown to be involved in energy metabolism, brain functions, inflammation and aging through its deacetylase activity, acting on both histone and non-histone substrates. In order to verify whether Sirt1 can replace Sir2p in the yeast cells, we expressed the full-length human Sirt1 protein in S.cerevisiae sir2Δ mutant strain. The structure of chromatin is basically maintained from yeast to human. Thus, yeast chromatin is a favourable environment to evaluate, inhibit or activate an ectopic histone deacetylase activity in an in vivo substrate. Mutant sir2Δ shows a series of different phenotypes, all dependent on the deacetylase activity of Sir2p. We analyzed the three silent loci where normally Sir2p acts: ribosomal DNA, telomeres and the mating type loci. Moreover, we verified extrachromosomal ribosomal DNA circles production and histone hyperacetylation levels, typical marks of sir2Δ strains. By strong SIRT1 overexpression in sir2Δ cells, we found that specific molecular phenotypes of the mutant revert almost to a wild-type condition. In particular, transcriptional silencing at rDNA was restored, extrachromosomal rDNA circles formation was repressed and histone acetylation at H3K9 and H4K16 decreased. The complementation at the other studied loci: HM loci, telomere and sub-telomere does not occur. Overall, our observations indicate that: i) SIRT1 gene is able to complement different molecular phenotypes of the sir2Δ mutant at rDNA ii) the in vivo screening of Sirt1 activity is possible in yeast.Davide GaglioAnna D'AlfonsoGiorgio CamilloniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83114 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Davide Gaglio Anna D'Alfonso Giorgio Camilloni Functional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.
description	Sirtuins, class III histone deacetylases, are proteins homologous to the yeast protein Sir2p. Mammalian Sirt1 has been shown to be involved in energy metabolism, brain functions, inflammation and aging through its deacetylase activity, acting on both histone and non-histone substrates. In order to verify whether Sirt1 can replace Sir2p in the yeast cells, we expressed the full-length human Sirt1 protein in S.cerevisiae sir2Δ mutant strain. The structure of chromatin is basically maintained from yeast to human. Thus, yeast chromatin is a favourable environment to evaluate, inhibit or activate an ectopic histone deacetylase activity in an in vivo substrate. Mutant sir2Δ shows a series of different phenotypes, all dependent on the deacetylase activity of Sir2p. We analyzed the three silent loci where normally Sir2p acts: ribosomal DNA, telomeres and the mating type loci. Moreover, we verified extrachromosomal ribosomal DNA circles production and histone hyperacetylation levels, typical marks of sir2Δ strains. By strong SIRT1 overexpression in sir2Δ cells, we found that specific molecular phenotypes of the mutant revert almost to a wild-type condition. In particular, transcriptional silencing at rDNA was restored, extrachromosomal rDNA circles formation was repressed and histone acetylation at H3K9 and H4K16 decreased. The complementation at the other studied loci: HM loci, telomere and sub-telomere does not occur. Overall, our observations indicate that: i) SIRT1 gene is able to complement different molecular phenotypes of the sir2Δ mutant at rDNA ii) the in vivo screening of Sirt1 activity is possible in yeast.
format	article
author	Davide Gaglio Anna D'Alfonso Giorgio Camilloni
author_facet	Davide Gaglio Anna D'Alfonso Giorgio Camilloni
author_sort	Davide Gaglio
title	Functional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.
title_short	Functional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.
title_full	Functional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.
title_fullStr	Functional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.
title_full_unstemmed	Functional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.
title_sort	functional complementation of sir2δ yeast mutation by the human orthologous gene sirt1.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9fcdef6a744448c1a7f0cabdb63ce364
work_keys_str_mv	AT davidegaglio functionalcomplementationofsir2dyeastmutationbythehumanorthologousgenesirt1 AT annadalfonso functionalcomplementationofsir2dyeastmutationbythehumanorthologousgenesirt1 AT giorgiocamilloni functionalcomplementationofsir2dyeastmutationbythehumanorthologousgenesirt1
_version_	1718421461361754112

Functional complementation of sir2Δ yeast mutation by the human orthologous gene SIRT1.

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