SIRT1 negatively regulates rRNA expression

Stable Identifier
Homo sapiens
Regulation of rRNA Expression by NAD-dependent Deacetylase Sirtuin-1
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Expression of rRNA genes is coupled to the overall metabolism of the cell by the NAD-dependent histone deacetylase SIRT1, a component of the Energy-dependent Nucleolar Silencing Complex (eNoSC) (Murayama et al. 2008, reviewed in Salminen and Kaarniranta 2009, Grummt and Voit 2010). eNoSC comprises Nucleomethylin (NML), SIRT1, and the histone methylase SUV39H1 (Murayama et al. 2008). Deacetylation and methylation of histone H3 in the chromatin of a rRNA gene by eNoSC causes reduced expression of the gene. When glucose is low, NAD is high (NADH is low), activity of SIRT1 is high, and activity of rRNA genes is reduced. It is hypothesized that eNoSC forms on a nucleosome containing dimethylated lysine-9 on histone H3 (H3K9me2) and then eNoSC deacetylates and dimethylates the adjacent nucleosome, thus catalyzing spreading of H3K9me2 throughout the gene.

Literature References
PubMed ID Title Journal Year
19010308 SIRT1 regulates the ribosomal DNA locus: epigenetic candles twinkle longevity in the Christmas tree

Salminen, A, Kaarniranta, K

Biochem. Biophys. Res. Commun. 2009
18485871 Epigenetic control of rDNA loci in response to intracellular energy status

Murayama, A, Ohmori, K, Fujimura, A, Minami, H, Yasuzawa-Tanaka, K, Kuroda, T, Oie, S, Daitoku, H, Okuwaki, M, Nagata, K, Fukamizu, A, Kimura, K, Shimizu, T, Yanagisawa, J

Cell 2008
20023389 Linking rDNA transcription to the cellular energy supply

Grummt, I, Voit, R

Cell Cycle 2010
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Orthologous Events