Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus.
BACKGROUND
Genes encoding the circadian pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) of mammals have recently been identified, but the molecular basis of circadian timing in peripheral tissue is not well understood. We used a custom-made cDNA microarray to identify mouse liver transcripts that show circadian cycles of abundance under constant conditions.


RESULTS
Using two independent tissue sampling and hybridization regimes, we show that approximately 9% of the 2122 genes studied show robust circadian cycling in the liver. These transcripts were categorized by their phase of abundance, defining clusters of day- and night-related genes, and also by the function of their products. Circadian regulation of genes was tissue specific, insofar as novel rhythmic liver genes were not necessarily rhythmic in the brain, even when expressed in the SCN. The rhythmic transcriptome in the periphery is, nevertheless, dependent on the SCN because surgical ablation of the SCN severely dampened or destroyed completely the cyclical expression of both canonical circadian genes and novel genes identified by microarray analysis.


CONCLUSIONS
Temporally complex, circadian programming of the transcriptome in a peripheral organ is imposed across a wide range of core cellular functions and is dependent on an interaction between intrinsic, tissue-specific factors and extrinsic regulation by the SCN central pacemaker.
Akhtar
Ruth A
RA
Department of Genetics, University of Leicester, LE1 7RH, Leicester, United Kingdom.
Reddy
Akhilesh B
AB
Maywood
Elizabeth S
ES
Clayton
Jonathan D
JD
King
Verdun M
VM
Smith
Andrew G
AG
Gant
Timothy W
TW
Hastings
Michael H
MH
Kyriacou
Charalambos P
CP
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D015870:Gene Expression; D017403:In Situ Hybridization / Q000379:methods; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D014158:Transcription, Genetic