Document Detail

DEC1 modulates the circadian phase of clock gene expression.
MedLine Citation:
PMID:  18411297     Owner:  NLM     Status:  MEDLINE    
DEC1 suppresses CLOCK/BMAL1-enhanced promoter activity, but its role in the circadian system of mammals remains unclear. Here we examined the effect of Dec1 overexpression or deficiency on circadian gene expression triggered with 50% serum. Overexpression of Dec1 delayed the phase of clock genes such as Dec1, Dec2, Per1, and Dbp that contain E boxes in their regulatory regions, whereas it had little effect on the circadian phase of Per2 and Cry1 carrying CACGTT E' boxes. In contrast, Dec1 deficiency advanced the phase of the E-box-containing clock genes but not that of the E'-box-containing clock genes. Accordingly, DEC1 showed strong binding and transrepression on the E box, but not on the E' box, in chromatin immunoprecipitation, electrophoretic mobility shift, and luciferase reporter assays. Dec1-/- mice showed behavioral rhythms with slightly but significantly longer circadian periods under conditions of constant darkness and faster reentrainment to a 6-h phase-advanced shift of a light-dark cycle. Knockdown of Dec2 with small interfering RNA advanced the phase of Dec1 and Dbp expression, and double knockdown of Dec1 and Dec2 had much stronger effects on the expression of the E-box-containing clock genes. These findings suggest that DEC1, along with DEC2, plays a role in the finer regulation and robustness of the molecular clock.
Ayumu Nakashima; Takeshi Kawamoto; Kiyomasa K Honda; Taichi Ueshima; Mitsuhide Noshiro; Tomoyuki Iwata; Katsumi Fujimoto; Hiroshi Kubo; Sato Honma; Noriaki Yorioka; Nobuoki Kohno; Yukio Kato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-14
Journal Detail:
Title:  Molecular and cellular biology     Volume:  28     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-02     Completed Date:  2008-07-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4080-92     Citation Subset:  IM    
Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan.
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MeSH Terms
ARNTL Transcription Factors
Basic Helix-Loop-Helix Transcription Factors / genetics*,  metabolism,  physiology*
CLOCK Proteins
Circadian Rhythm
Gene Expression Regulation*
Homeodomain Proteins / genetics*,  physiology*
Mice, Transgenic
NIH 3T3 Cells
Stem Cells / cytology
Trans-Activators / metabolism*
Tumor Suppressor Proteins / genetics*,  physiology*
Reg. No./Substance:
0/ARNTL Transcription Factors; 0/ARNTL protein, human; 0/Arntl protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Bhlhb2 protein, mouse; 0/DEC1 protein, human; 0/Homeodomain Proteins; 0/Trans-Activators; 0/Tumor Suppressor Proteins; EC Proteins; EC protein, human; EC protein, mouse

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