Tissue-specific disruption of rhythmic expression of Dec1 and Dec2 in clock mutant mice.
DEC1 and DEC2-basic helix-loop-helix transcription factors-exhibit a circadian expression in the suprachiasmatic nucleus and other peripheral tissues and seem to play roles in regulating the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoters of Per1, Dec1, and Dec2. The authors present data on the expression patterns of mRNA for Dec1, Dec2, Per2, Dbp, and Npas2 in various tissues of wild-type and homozygous Clock mutant mice (Clock/Clock). The Clock mutation resulted in extreme reduction of Dec1 expression in kidney, heart, and skeletal muscle but not in liver, whereas it strongly repressed Dec2 expression in liver, kidney, and heart, while Dec2 expression in skeletal muscle remained rhythmic. Per2 also showed the tissue-dependent disruption of the rhythmicity by Clock mutation, whereas rhythmic expression of Dbp in Clock mutant mice disappeared in all tissues examined. Npas2, a structurally and functionally related gene to Clock, showed significant levels of expression in the liver and kidney with a robust rhythmicity, which was also affected by Clock mutation. These marked changes in the Dec1 and Dec2 expression, as well as in the Per2, Dbp, and Npas2 expression in the periphery by Clock mutation, indicated that CLOCK plays a major role in the expression of these genes in most tissues. However, circadian expression of Dec1 in liver and kidney and that of Dec2 in skeletal muscle of Clock mutant mice suggested that CLOCK-independent circadian regulation operates in some tissues.
Noshiro
Mitsuhide
M
Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. noshiro@hiroshima-u.ac.jp
Furukawa
Masae
M
Honma
Sato
S
Kawamoto
Takeshi
T
Hamada
Taizo
T
Honma
Ken-ichi
K
Kato
Yukio
Y
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D011401:Promoter Regions, Genetic; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C470968:Bhlhb3 protein, mouse; C491539:Bhlhe40 protein, mouse; C498260:Dbp protein, mouse; C491259:Npas2 protein, mouse; C421902:PER2 protein, human; C513312:Per2 protein, mouse; C538943:CLOCK protein, human; C538944:Clock protein, mouse