Circadian rhythms are essential to health. Their disru
ption is associated with metabolic diseases in ex
perimental animals and man
1,
2 and
3. Local metabolic rhythms re
present an out
put of tissue-based circadian clocks
[4]. Attem
pts to define how local metabolism is tem
porally coordinated have focused on gene ex
pression by defining extensive and divergent “circadian transcri
ptomes” involving 5 % –10 % of genes assayed
5,
6,
7 and
8. These analyses are inevitably incom
plete, not least because metabolic coordination de
pends ultimately u
pon tem
poral regulation of
proteins
9 and
10. We therefore conducted a systematic analysis of a mammalian “circadian
proteome.” Our analysis revealed that u
p to 20 % of soluble
proteins assayed in mouse liver are subject to circadian control. Many of these circadian
proteins are novel and cluster into discrete
phase grou
ps so that the liver's enzymatic
profile contrasts dramatically between day and night. Unex
pectedly, almost half of the cycling
proteins lack a corres
ponding cycling transcri
pt, as determined by quantitative PCR, microarray, or both and revealing for the first time the extent of
posttranscri
ptional mechanisms as circadian control
points. The circadian
proteome includes rate-limiting factors in vital
pathways, including urea formation and sugar metabolism. These findings
provide a new
pers
pective on the extensive contribution of circadian
programming to he
patic
physiology.