A transcription factor
response element for gene expression during circadian night
Ueda H R, Chen W, Adachi A, Wakamatsu H, Hayashi S, Takasugi T, Nagano
M, Nakahama K, Suzuki Y, Sugano S, Iino M, Shigeyoshi Y and Hashimoto
S
Nature 418(6897):534-9 (2002)
SUMMARY
Mammalian circadian clocks consist of complex integrated feedback loops
that cannot be elucidated without comprehensive measurement of system
dynamics and determination of network structures. To dissect such a complicated
system, we took a systems-biological approach based on genomic, molecular
and cell biological techniques. We profiled suprachiasmatic nuclei and
liver genome-wide expression patterns under light/dark cycles and constant
darkness. We determined transcription start sites of human orthologues
for newly identified cycling genes and then performed bioinformatical
searches for relationships between time-of-day specific expression and
transcription factor response elements around transcription start sites.
Here we demonstrate the role of the Rev-ErbA/ROR response element in gene
expression during circadian night, which is in phase with Bmal1 and in
antiphase to Per2 oscillations. This role was verified using an in vitro
validation system, in which cultured fibroblasts transiently transfected
with clock-controlled reporter vectors exhibited robust circadian bioluminescence.
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