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Role of SIRT1 in Epigenetics

  • Zhipeng A. Wang
  • Willie Hsu
  • Wenshe R. Liu
Reference work entry

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.

Keywords

Sirtuin Epigenetics Lysine Histone Acetylation Nicotinamide Nucleosome Posttranslational modification Transcription factor Metabolism 

List of 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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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of ChemistryTexas A&M UniversityCollege StationUSA

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