PMID:20439498

Citation	Li, M, Petteys, BJ, McClure, JM, Valsakumar, V, Bekiranov, S, Frank, EL and Smith, JS (2010) Thiamine biosynthesis in Saccharomyces cerevisiae is regulated by the NAD+-dependent histone deacetylase Hst1. Mol. Cell. Biol. 30:3329-41
Abstract	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 THI gene promoters that does not overlap with a previously defined enhancer region bound by the thiamine-responsive Thi2/Thi3/Pdc2 transcriptional activators. The specificity of histone H3 and/or H4 deacetylation carried out by Hst1 and Sir2 at the distal promoter region depends on the THI gene being tested. Hst1/Sir2-mediated repression of the THI genes occurs at the level of basal expression, thus representing the first set of transcription factors shown to actively repress this gene class. Importantly, lowering the NAD(+) concentration and inhibiting the Hst1/Sum1 HDAC complex elevated the intracellular thiamine concentration due to increased thiamine biosynthesis and transport, implicating NAD(+) in the control of thiamine homeostasis.
Links	PubMed PMC2897578 Online version:10.1128/MCB.01590-09
Keywords	Animals; Gene Expression Profiling; Gene Expression Regulation, Fungal; Humans; Microarray Analysis; Molecular Structure; NAD/metabolism; Pentosyltransferases/genetics; Pentosyltransferases/metabolism; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Sirtuin 2/genetics; Sirtuin 2/metabolism; Sirtuins/genetics; Sirtuins/metabolism; Thiamine/biosynthesis
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:HST1		GO:0070623: regulation of thiamine biosynthetic process	ECO:0000315:		P		Figure 7A illusterates an increase in intracellular thiamine levels in the mutant Hst1 representing that cellular thiamine homeostasis in yeast requires Hst1.	complete CACAO 4730
YEAST:HST1	involved_in	GO:0070623: regulation of thiamine biosynthetic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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