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Role of SIRT1 in Epigenetics

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Handbook of Nutrition, Diet, and Epigenetics

Abstract

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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Abbreviations

AA:

Amino acid residues

AADPR:

O-Acetyl ADP ribose

AcK:

Acetyllysine

ATM:

Ataxia-telangiectasia mutated

BESTO:

β-Cell-specific SIRT1 overexpressing

CTIP2:

Chicken ovalbumin upstream promoter-transcription factor-interacting protein 2

DNMT:

DNA methyltransferase

DSBs:

DNA double-strand breaks

ELISA:

Enzyme-linked immunosorbent assay

ERRs:

Estrogen receptor-related receptors

FH:

Facultative heterochromatin

FOXA2:

Forkhead box protein A2

Gal4:

Yeast transcription activator protein Gal4

H3K9Ac, H3K14Ac, H4K16Ac, etc.:

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

HDACs:

Histone deacetylases

hMOF:

Histone acetyltransferase human MOF

NAD+:

Nicotinamide adenine dinucleotide oxidative form

ncAA:

Noncanonical amino acid incorporation

NCL:

Native chemical ligation

PDX1:

Pancreas duodenum homeobox 1

PTM:

Posttranslational modification

SIR:

Yeast-silencing information regulator

SIRT1:

Sirtuin 1

SMILE:

Small heterodimer partner-interacting leucine zipper protein

SPPS:

Solid-phase peptide synthesis

SUMO:

Small ubiquitin-like modifier protein

SUV39H1:

Suppressor of variegation 3-9 homologue 1

TIP5:

Transcription termination factor I-interacting protein 5

TIP60:

Tat-interactive protein

TLE1:

Transducin-like enhancer of split-1

UCP2:

Uncoupling protein 2

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Correspondence to Wenshe R. Liu .

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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. https://doi.org/10.1007/978-3-319-55530-0_1

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