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Dec1 and Dec2 are regulators of the mammalian molecular clock

Author

Listed:
  • 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)

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.

Suggested Citation

  • Sato Honma & Takeshi Kawamoto & Yumiko Takagi & Katsumi Fujimoto & Fuyuki Sato & Mitsuhide Noshiro & Yukio Kato & Ken-ichi Honma, 2002. "Dec1 and Dec2 are regulators of the mammalian molecular clock," Nature, Nature, vol. 419(6909), pages 841-844, October.
  • Handle: RePEc:nat:nature:v:419:y:2002:i:6909:d:10.1038_nature01123
    DOI: 10.1038/nature01123
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    Cited by:

    1. Anna Podleśny-Drabiniok & Gloriia Novikova & Yiyuan Liu & Josefine Dunst & Rose Temizer & Chiara Giannarelli & Samuele Marro & Taras Kreslavsky & Edoardo Marcora & Alison Mary Goate, 2024. "BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer’s disease and other disorders of lipid-rich tissues," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Hassan M Fathallah-Shaykh, 2010. "Dynamics of the Drosophila Circadian Clock: Theoretical Anti-Jitter Network and Controlled Chaos," PLOS ONE, Public Library of Science, vol. 5(10), pages 1-7, October.
    3. Hao A. Duong & Kenkichi Baba & Jason P. DeBruyne & Alec J. Davidson & Christopher Ehlen & Michael Powell & Gianluca Tosini, 2024. "Environmental circadian disruption re-writes liver circadian proteomes," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Lasse K. Markussen & Elizabeth A. Rondini & Olivia Sveidahl Johansen & Jesper G. S. Madsen & Elahu G. Sustarsic & Ann-Britt Marcher & Jacob B. Hansen & Zachary Gerhart-Hines & James G. Granneman & Sus, 2022. "Lipolysis regulates major transcriptional programs in brown adipocytes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Patty C Kandalepas & Jennifer W Mitchell & Martha U Gillette, 2016. "Melatonin Signal Transduction Pathways Require E-Box-Mediated Transcription of Per1 and Per2 to Reset the SCN Clock at Dusk," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-18, June.

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