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Role of SIRT1 in Epigenetics

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Handbook of Nutrition, Diet, and Epigenetics


Epigenetic markers are of great significance in biological systems closely related to genome stability, gene transcription, metabolic regulation, and human diseases. Sirtuins are specially named NAD+-dependent class III histone deacetylases that can catalyze the deacylation of modified lysines, which exist as a major group of posttranslational modifications (PTMs) on both nucleic and cytoplasmic proteins. Among the seven sirtuin enzymes 1–7, sirtuin 1 (SIRT1) can catalyze the deacetylation reaction on both histones and many important nonhistone proteins, serving as a key conjunction between epigenetics, metabolism, and human health. In this chapter, we will begin with the basic introduction of SIRT1 biochemistry and its enzymatic mechanism, followed by the discussion on in vitro deacetylation assays. The biological functions of SIRT1 will be categorized into three main groups based on its substrates. Directly involved in many important cellular procedures, SIRT1 builds up the connection between epigenetics and metabolism. Since SIRT1 is important to human health, its activation and inhibition can be one of the potential treatment targets for diseases such as cancer and neurodegeneration. Our analysis is aiming to provide some new aspects into the biochemistry and chemical biology of SIRT1.

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Amino acid residues


O-Acetyl ADP ribose




Ataxia-telangiectasia mutated


β-Cell-specific SIRT1 overexpressing


Chicken ovalbumin upstream promoter-transcription factor-interacting protein 2


DNA methyltransferase


DNA double-strand breaks


Enzyme-linked immunosorbent assay


Estrogen receptor-related receptors


Facultative heterochromatin


Forkhead box protein A2


Yeast transcription activator protein Gal4

H3K9Ac, H3K14Ac, H4K16Ac, etc.:

(H3 at lysine 9 site, 14 site, 16 site, etc.)


Histone deacetylases


Histone acetyltransferase human MOF


Nicotinamide adenine dinucleotide oxidative form


Noncanonical amino acid incorporation


Native chemical ligation


Pancreas duodenum homeobox 1


Posttranslational modification


Yeast-silencing information regulator


Sirtuin 1


Small heterodimer partner-interacting leucine zipper protein


Solid-phase peptide synthesis


Small ubiquitin-like modifier protein


Suppressor of variegation 3-9 homologue 1


Transcription termination factor I-interacting protein 5


Tat-interactive protein


Transducin-like enhancer of split-1


Uncoupling protein 2


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Wang, Z.A., Hsu, W., Liu, W.R. (2019). Role of SIRT1 in Epigenetics. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham.

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