title: A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation.
abstract: An autofeedback loop associated with transcription of clock gene(s), Per(s), is generally accepted as the molecular machinery of circadian rhythm generation, in which CLOCK/BMAL act as positive regulators and PER/CRY as negative ones. We show here an autofeedback loop of Dec1 encoding a basic helix-loop-helix transcription factor: CLOCK/BMAL increased the promoter activity of Dec1, and DEC1 and DEC2 as well as PERs and CRYs suppressed the induced expression. Three CACGTG E-boxes are responsible for both the activation and the suppression of Dec1 transcription. Forced expression of Clock/Bmal increased endogenous Dec1 mRNA level, and overexpression of Dec1 resulted in suppression of Dec2, Per2, and Dbp expression. The level of Dec1 expression in the heart of Clock/Clock mutant mice was continuously low throughout the day. These findings suggest that Dec1 is positively regulated by CLOCK/BMAL and is involved in circadian rhythm regulation by suppressing CLOCK/BMAL-induced gene expression. The autofeedback loop of Dec1 may be interlocked with the core feedback loop of Per in some situations.
authors.affiliation: Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Noshiro
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Sato
authors.forename: Koji
authors.initials: K
authors.lastname: Maemura
authors.forename: Norihiko
authors.initials: N
authors.lastname: Takeda
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Iwata
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Masae
authors.initials: M
authors.lastname: Furukawa
authors.forename: Kazuko
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Sato
authors.initials: S
authors.lastname: Honma
authors.forename: Ken ichi
authors.initials: Ki
authors.lastname: Honma
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology*; D025461:Feedback, Physiological; D015870:Gene Expression; D018257:Helix-Loop-Helix Motifs; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D008156:Luciferases; D014157:Transcription Factors; C107989:BHLHE40 protein, human; C491539:Bhlhe40 protein, mouse