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dc.contributor.authorLatham, Tom
dc.contributor.authorMackay, Logan
dc.contributor.authorSproul, Duncan
dc.contributor.authorKarim, Muhammed
dc.contributor.authorCulley, Jayne
dc.contributor.authorHarrison, David J.
dc.contributor.authorHayward, Larry
dc.contributor.authorLangridge-Smith, Pat
dc.contributor.authorGilbert, Nick
dc.contributor.authorRamsahoye, Bernard H.
dc.identifier.citationLatham , T , Mackay , L , Sproul , D , Karim , M , Culley , J , Harrison , D J , Hayward , L , Langridge-Smith , P , Gilbert , N & Ramsahoye , B H 2012 , ' Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression ' , Nucleic Acids Research , vol. 40 , no. 11 , pp. 4794-4803 .
dc.identifier.otherPURE: 25744507
dc.identifier.otherPURE UUID: 2df6ca8c-81a8-4d96-931c-9bfe70375905
dc.identifier.otherWOS: 000305032500016
dc.identifier.otherScopus: 84862229806
dc.identifier.otherORCID: /0000-0001-9041-9988/work/64034219
dc.description.abstractChemical inhibitors of histone deacetylase (HDAC) activity are used as experimental tools to induce histone hyperacetylation and deregulate gene transcription, but it is not known whether the inhibition of HDACs plays any part in the normal physiological regulation of transcription. Using both in vitro and in vivo assays, we show that lactate, which accumulates when glycolysis exceeds the cell's aerobic metabolic capacity, is an endogenous HDAC inhibitor, deregulating transcription in an HDAC-dependent manner. Lactate is a relatively weak inhibitor (IC50 40 mM) compared to the established inhibitors trichostatin A and butyrate, but the genes deregulated overlap significantly with those affected by low concentrations of the more potent inhibitors. HDAC inhibition causes significant up and downregulation of genes, but genes that are associated with HDAC proteins are more likely to be upregulated and less likely to be downregulated than would be expected. Our results suggest that the primary effect of HDAC inhibition by endogenous short-chain fatty acids like lactate is to promote gene expression at genes associated with HDAC proteins. Therefore, we propose that lactate may be an important transcriptional regulator, linking the metabolic state of the cell to gene transcription.
dc.relation.ispartofNucleic Acids Researchen
dc.rights© The Author(s) 2012. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectGlycolytic matabolismen
dc.subjectHistone deacetylase (HDAC)en
dc.subjectGene expressionen
dc.titleLactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expressionen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.description.statusPeer revieweden

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