SIRT1-dependent regulation of chromatin and transcription

Linking NAD+ metabolism and signaling to the control of cellular functions

Tong Zhang, W. Lee Kraus

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

Sirtuins comprise a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases. Mammalian SIRT1 - a homolog of yeast Sir2, the prototypical member of the sirtuin family - is an important regulator of metabolism, cell differentiation and senescence, stress response, and cancer. As an NAD+-dependent enzyme, SIRT1 regulates gene expression programs in response to cellular metabolic status, thereby coordinating metabolic adaptation of the whole organism. Several important mechanisms have emerged for SIRT1-dependent regulation of transcription. First, SIRT1 can modulate chromatin function through direct deacetylation of histones as well as by promoting alterations in the methylation of histones and DNA, leading to the repression of transcription. The latter is accomplished through the recruitment of other nuclear enzymes to chromatin for histone methylation and DNA CpG methylation, suggesting a broader role of SIRT1 in epigenetic regulation. Second, SIRT1 can interact and deacetylate a broad range of transcription factors and coregulators, thereby regulating target gene expression both positively and negatively. Cellular energy state, specifically NAD+ metabolism, plays a major role in the regulation of SIRT1 activity. Recent studies on the NAD+ biosynthetic enzymes in the salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1), have revealed important functions for these enzymes in SIRT1-dependent transcription regulation. The collective molecular actions of SIRT1 control specific patterns of gene expression that modulate a wide variety of physiological outcomes.

Original languageEnglish (US)
Pages (from-to)1666-1675
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1804
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Transcription
Metabolism
NAD
Chromatin
Gene expression
Histones
Methylation
DNA Methylation
Enzymes
Gene Expression
Nicotinamide-Nucleotide Adenylyltransferase
Sirtuins
Nicotinamide Phosphoribosyltransferase
ADP Ribose Transferases
Salvaging
Cell Aging
Epigenomics
Yeast
Electron energy levels
Cell Differentiation

Keywords

  • Chromatin
  • Deacetylation
  • Metabolism
  • NAD
  • SIRT1
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

Cite this

@article{5541311982884d9d9c1f3c334b18f88a,
title = "SIRT1-dependent regulation of chromatin and transcription: Linking NAD+ metabolism and signaling to the control of cellular functions",
abstract = "Sirtuins comprise a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases. Mammalian SIRT1 - a homolog of yeast Sir2, the prototypical member of the sirtuin family - is an important regulator of metabolism, cell differentiation and senescence, stress response, and cancer. As an NAD+-dependent enzyme, SIRT1 regulates gene expression programs in response to cellular metabolic status, thereby coordinating metabolic adaptation of the whole organism. Several important mechanisms have emerged for SIRT1-dependent regulation of transcription. First, SIRT1 can modulate chromatin function through direct deacetylation of histones as well as by promoting alterations in the methylation of histones and DNA, leading to the repression of transcription. The latter is accomplished through the recruitment of other nuclear enzymes to chromatin for histone methylation and DNA CpG methylation, suggesting a broader role of SIRT1 in epigenetic regulation. Second, SIRT1 can interact and deacetylate a broad range of transcription factors and coregulators, thereby regulating target gene expression both positively and negatively. Cellular energy state, specifically NAD+ metabolism, plays a major role in the regulation of SIRT1 activity. Recent studies on the NAD+ biosynthetic enzymes in the salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1), have revealed important functions for these enzymes in SIRT1-dependent transcription regulation. The collective molecular actions of SIRT1 control specific patterns of gene expression that modulate a wide variety of physiological outcomes.",
keywords = "Chromatin, Deacetylation, Metabolism, NAD, SIRT1, Transcription",
author = "Tong Zhang and Kraus, {W. Lee}",
year = "2010",
month = "8",
doi = "10.1016/j.bbapap.2009.10.022",
language = "English (US)",
volume = "1804",
pages = "1666--1675",
journal = "Biochimica et Biophysica Acta - Proteins and Proteomics",
issn = "1570-9639",
publisher = "Elsevier",
number = "8",

}

TY - JOUR

T1 - SIRT1-dependent regulation of chromatin and transcription

T2 - Linking NAD+ metabolism and signaling to the control of cellular functions

AU - Zhang, Tong

AU - Kraus, W. Lee

PY - 2010/8

Y1 - 2010/8

N2 - Sirtuins comprise a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases. Mammalian SIRT1 - a homolog of yeast Sir2, the prototypical member of the sirtuin family - is an important regulator of metabolism, cell differentiation and senescence, stress response, and cancer. As an NAD+-dependent enzyme, SIRT1 regulates gene expression programs in response to cellular metabolic status, thereby coordinating metabolic adaptation of the whole organism. Several important mechanisms have emerged for SIRT1-dependent regulation of transcription. First, SIRT1 can modulate chromatin function through direct deacetylation of histones as well as by promoting alterations in the methylation of histones and DNA, leading to the repression of transcription. The latter is accomplished through the recruitment of other nuclear enzymes to chromatin for histone methylation and DNA CpG methylation, suggesting a broader role of SIRT1 in epigenetic regulation. Second, SIRT1 can interact and deacetylate a broad range of transcription factors and coregulators, thereby regulating target gene expression both positively and negatively. Cellular energy state, specifically NAD+ metabolism, plays a major role in the regulation of SIRT1 activity. Recent studies on the NAD+ biosynthetic enzymes in the salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1), have revealed important functions for these enzymes in SIRT1-dependent transcription regulation. The collective molecular actions of SIRT1 control specific patterns of gene expression that modulate a wide variety of physiological outcomes.

AB - Sirtuins comprise a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases. Mammalian SIRT1 - a homolog of yeast Sir2, the prototypical member of the sirtuin family - is an important regulator of metabolism, cell differentiation and senescence, stress response, and cancer. As an NAD+-dependent enzyme, SIRT1 regulates gene expression programs in response to cellular metabolic status, thereby coordinating metabolic adaptation of the whole organism. Several important mechanisms have emerged for SIRT1-dependent regulation of transcription. First, SIRT1 can modulate chromatin function through direct deacetylation of histones as well as by promoting alterations in the methylation of histones and DNA, leading to the repression of transcription. The latter is accomplished through the recruitment of other nuclear enzymes to chromatin for histone methylation and DNA CpG methylation, suggesting a broader role of SIRT1 in epigenetic regulation. Second, SIRT1 can interact and deacetylate a broad range of transcription factors and coregulators, thereby regulating target gene expression both positively and negatively. Cellular energy state, specifically NAD+ metabolism, plays a major role in the regulation of SIRT1 activity. Recent studies on the NAD+ biosynthetic enzymes in the salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 1 (NMNAT-1), have revealed important functions for these enzymes in SIRT1-dependent transcription regulation. The collective molecular actions of SIRT1 control specific patterns of gene expression that modulate a wide variety of physiological outcomes.

KW - Chromatin

KW - Deacetylation

KW - Metabolism

KW - NAD

KW - SIRT1

KW - Transcription

UR - http://www.scopus.com/inward/record.url?scp=77953290752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953290752&partnerID=8YFLogxK

U2 - 10.1016/j.bbapap.2009.10.022

DO - 10.1016/j.bbapap.2009.10.022

M3 - Article

VL - 1804

SP - 1666

EP - 1675

JO - Biochimica et Biophysica Acta - Proteins and Proteomics

JF - Biochimica et Biophysica Acta - Proteins and Proteomics

SN - 1570-9639

IS - 8

ER -