Mammalian circadian biology

Elucidating genome-wide levels of temporal organization

Phillip L. Lowrey, Joseph S. Takahashi

Research output: Contribution to journalArticle

674 Citations (Scopus)

Abstract

During the past decade, the molecular mechanisms underlying the mammalian circadian clock have been defined. A core set of circadian clock genes common to most cells throughout the body code for proteins that feed back to regulate not only their own expression, but also that of clock output genes and pathways throughout the genome. The circadian system represents a complex multioscillatory temporal network in which an ensemble of coupled neurons comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus is entrained to the daily light/dark cycle and subsequently transmits synchronizing signals to local circadian oscillators in peripheral tissues. Only recently has the importance of this system to the regulation of such fundamental biological processes as the cell cycle and metabolism become apparent. A convergence of data from microarray studies, quantitative trait locus analysis, and mutagenesis screens demonstrates the pervasiveness of circadian regulation in biological systems. The importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed by animal models in which mutations in genes coding for core components of the clock result in disease, including cancer and disturbances to the sleep/wake cycle.

Original languageEnglish (US)
Pages (from-to)407-441
Number of pages35
JournalAnnual Review of Genomics and Human Genetics
Volume5
DOIs
StatePublished - 2004

Fingerprint

Clocks
Circadian Clocks
Genes
Genome
Biological Phenomena
Suprachiasmatic Nucleus
Quantitative Trait Loci
Photoperiod
Mutagenesis
Pacemakers
Hypothalamus
Cell Cycle
Sleep
Homeostasis
Biological systems
Microarrays
Animal Models
Metabolism
Neurons
Mutation

Keywords

  • Circadian clock genes
  • Complex traits
  • ENU
  • Mutagenesis
  • Sleep-wake cycle
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Genetics(clinical)
  • Biochemistry
  • Genetics

Cite this

Mammalian circadian biology : Elucidating genome-wide levels of temporal organization. / Lowrey, Phillip L.; Takahashi, Joseph S.

In: Annual Review of Genomics and Human Genetics, Vol. 5, 2004, p. 407-441.

Research output: Contribution to journalArticle

@article{1b486e1a93e6413895e56727f7d4df02,
title = "Mammalian circadian biology: Elucidating genome-wide levels of temporal organization",
abstract = "During the past decade, the molecular mechanisms underlying the mammalian circadian clock have been defined. A core set of circadian clock genes common to most cells throughout the body code for proteins that feed back to regulate not only their own expression, but also that of clock output genes and pathways throughout the genome. The circadian system represents a complex multioscillatory temporal network in which an ensemble of coupled neurons comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus is entrained to the daily light/dark cycle and subsequently transmits synchronizing signals to local circadian oscillators in peripheral tissues. Only recently has the importance of this system to the regulation of such fundamental biological processes as the cell cycle and metabolism become apparent. A convergence of data from microarray studies, quantitative trait locus analysis, and mutagenesis screens demonstrates the pervasiveness of circadian regulation in biological systems. The importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed by animal models in which mutations in genes coding for core components of the clock result in disease, including cancer and disturbances to the sleep/wake cycle.",
keywords = "Circadian clock genes, Complex traits, ENU, Mutagenesis, Sleep-wake cycle, Suprachiasmatic nucleus",
author = "Lowrey, {Phillip L.} and Takahashi, {Joseph S.}",
year = "2004",
doi = "10.1146/annurev.genom.5.061903.175925",
language = "English (US)",
volume = "5",
pages = "407--441",
journal = "Annual Review of Genomics and Human Genetics",
issn = "1527-8204",
publisher = "Annual Reviews Inc.",

}

TY - JOUR

T1 - Mammalian circadian biology

T2 - Elucidating genome-wide levels of temporal organization

AU - Lowrey, Phillip L.

AU - Takahashi, Joseph S.

PY - 2004

Y1 - 2004

N2 - During the past decade, the molecular mechanisms underlying the mammalian circadian clock have been defined. A core set of circadian clock genes common to most cells throughout the body code for proteins that feed back to regulate not only their own expression, but also that of clock output genes and pathways throughout the genome. The circadian system represents a complex multioscillatory temporal network in which an ensemble of coupled neurons comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus is entrained to the daily light/dark cycle and subsequently transmits synchronizing signals to local circadian oscillators in peripheral tissues. Only recently has the importance of this system to the regulation of such fundamental biological processes as the cell cycle and metabolism become apparent. A convergence of data from microarray studies, quantitative trait locus analysis, and mutagenesis screens demonstrates the pervasiveness of circadian regulation in biological systems. The importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed by animal models in which mutations in genes coding for core components of the clock result in disease, including cancer and disturbances to the sleep/wake cycle.

AB - During the past decade, the molecular mechanisms underlying the mammalian circadian clock have been defined. A core set of circadian clock genes common to most cells throughout the body code for proteins that feed back to regulate not only their own expression, but also that of clock output genes and pathways throughout the genome. The circadian system represents a complex multioscillatory temporal network in which an ensemble of coupled neurons comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus is entrained to the daily light/dark cycle and subsequently transmits synchronizing signals to local circadian oscillators in peripheral tissues. Only recently has the importance of this system to the regulation of such fundamental biological processes as the cell cycle and metabolism become apparent. A convergence of data from microarray studies, quantitative trait locus analysis, and mutagenesis screens demonstrates the pervasiveness of circadian regulation in biological systems. The importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed by animal models in which mutations in genes coding for core components of the clock result in disease, including cancer and disturbances to the sleep/wake cycle.

KW - Circadian clock genes

KW - Complex traits

KW - ENU

KW - Mutagenesis

KW - Sleep-wake cycle

KW - Suprachiasmatic nucleus

UR - http://www.scopus.com/inward/record.url?scp=4544362674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544362674&partnerID=8YFLogxK

U2 - 10.1146/annurev.genom.5.061903.175925

DO - 10.1146/annurev.genom.5.061903.175925

M3 - Article

VL - 5

SP - 407

EP - 441

JO - Annual Review of Genomics and Human Genetics

JF - Annual Review of Genomics and Human Genetics

SN - 1527-8204

ER -