Mammalian circadian biology: Elucidating genome-wide levels of temporal organization

Phillip L. Lowrey, Joseph S. Takahashi

Research output: Contribution to journalReview article

690 Scopus citations

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 - Oct 25 2004

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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