Dec1 and Dec2 are regulators of the mammalian molecular clock

Sato Honma (), Takeshi Kawamoto, Yumiko Takagi, Katsumi Fujimoto, Fuyuki Sato, Mitsuhide Noshiro, Yukio Kato and Ken-ichi Honma
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Sato Honma: Hokkaido University Graduate School of Medicine
Takeshi Kawamoto: Hiroshima University Graduate School of Biomedical Sciences
Yumiko Takagi: Hokkaido University Graduate School of Medicine
Katsumi Fujimoto: Hiroshima University Graduate School of Biomedical Sciences
Fuyuki Sato: Hiroshima University Graduate School of Biomedical Sciences
Mitsuhide Noshiro: Hiroshima University Graduate School of Biomedical Sciences
Yukio Kato: Hiroshima University Graduate School of Biomedical Sciences
Ken-ichi Honma: Hokkaido University Graduate School of Medicine

Nature, 2002, vol. 419, issue 6909, 841-844

Abstract: Abstract The circadian rhythms in mammals are regulated by a pacemaker located in the suprachiasmatic nucleus of the hypothalamus1,2. Four clock-gene families have been found to be involved in a transcription–translation feedback loop that generates the circadian rhythm at the intracellular level3. The proteins Clock and Bmal1 form a heterodimer which activates the transcription of the Per gene from the E-box elements in its promoter region4,5. Protein products of Per act together with Cry proteins to inhibit Per transcription6,7, thus closing the autoregulatory feedback loop. We found that Dec1 and Dec2, basic helix–loop–helix transcription factors, repressed Clock/Bmal1-induced transactivation of the mouse Per1 promoter through direct protein–protein interactions with Bmal1 and/or competition for E-box elements. Dec1 and Dec2 are expressed in the suprachiasmic nucleus in a circadian fashion, with a peak in the subjective day. A brief light pulse induced Dec1 but not Dec2 expression in the suprachiasmic nucleus in a phase-dependent manner. Dec1 and Dec2 are regulators of the mammalian molecular clock, and form a fifth clock-gene family.

Date: 2002
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DOI: 10.1038/nature01123

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