Unknown,Transcriptomics,Genomics,Proteomics

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Yeast expression data from conditions that inhibit sirtuins


ABSTRACT: Sir2 is an NAD+-dependent histone deacetylase, and is the founding member of a large, phylogentically conserved, family of such deacetylases called the Sirtuins. The budding yeast, Saccharomyces cerevisiae, harbors 4 paralogs of Sir2, known as Hst1, Hst2, Hst3, and Hst4. Reducing the intracellular NAD+ concentration is inhibitory for the Sirtuins, and raising the intracellular nicotinamide (NAM) concentration is inhibitory. Microarray gene expression analysis was used to identify novel classes of yeast genes whose expression is altered when either NAD+ concentration is reduced or NAM is elevated. A subset of genes involved in thiamine biosynthesis was identified as being upregulated when Sir2 or Hst1 was inactivated. Several mutants in the NAD+ biosynthesis and salvage pathways were tested, along with WT and WT grown in the presence of 5 mM nicotinamide, which inhibits the Sirtuins. Duplicate cultures in rich YPD media were grown into log phase and then harvested. The deletion mutants npt1M-bM-^HM-^F, bna1M-bM-^HM-^F, tna1M-bM-^HM-^F, and pnc1M-bM-^HM-^F were compared to a wild-type (WT) strain. Additionally, a WT strain grown in the presence of 5 mM NAM was compared to WT without NAM. Total RNA was isolated and used for microarray hybridizations onto Affymetrix Yeast 2.0 Gene arrrays.

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Veena Valsakumar 

PROVIDER: E-GEOD-18488 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Thiamine biosynthesis in Saccharomyces cerevisiae is regulated by the NAD+-dependent histone deacetylase Hst1.

Li Mingguang M   Petteys Brian J BJ   McClure Julie M JM   Valsakumar Veena V   Bekiranov Stefan S   Frank Elizabeth L EL   Smith Jeffrey S JS  

Molecular and cellular biology 20100503 13


Genes encoding thiamine biosynthesis enzymes in microorganisms are tightly regulated such that low environmental thiamine concentrations activate transcription and high concentrations are repressive. We have determined that multiple thiamine (THI) genes in Saccharomyces cerevisiae are also regulated by the intracellular NAD(+) concentration via the NAD(+)-dependent histone deacetylase (HDAC) Hst1 and, to a lesser extent, Sir2. Both of these HDACs associate with a distal region of the affected TH  ...[more]

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