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
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U2 - 10.1146/annurev.genom.5.061903.175925
DO - 10.1146/annurev.genom.5.061903.175925
M3 - Review article
C2 - 15485355
AN - SCOPUS:4544362674
SN - 1527-8204
VL - 5
SP - 407
EP - 441
JO - Annual Review of Genomics and Human Genetics
JF - Annual Review of Genomics and Human Genetics
ER -