title: A positive role for PERIOD in mammalian circadian gene expression.
abstract: In the current model of the mammalian circadian clock, PERIOD (PER) represses the activity of the circadian transcription factors BMAL1 and CLOCK, either independently or together with CRYPTOCHROME (CRY). Here, we provide evidence that PER has an entirely different function from that reported previously, namely, that PER inhibits CRY-mediated transcriptional repression through interference with CRY recruitment into the BMAL1-CLOCK complex. This indirect positive function of PER is consistent with previous data from genetic analyses using Per-deficient or mutant mice. Overall, our results support the hypothesis that PER plays different roles in different circadian phases: an early phase in which it suppresses CRY activity, and a later phase in which it acts as a transcriptional repressor with CRY. This buffering effect of PER on CRY might help to prolong the period of rhythmic gene expression. Additional studies are required to carefully examine the promoter- and phase-specific roles of PER.
authors.affiliation: The Research Institute for Time Studies, Yamaguchi University, Yamaguchi 753-8511, Japan. Electronic address: akashima@yamaguchi-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Akashi
authors.affiliation: The Research Institute for Time Studies, Yamaguchi University, Yamaguchi 753-8511, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tsuchiya
authors.affiliation: Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Todo
authors.affiliation: Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Nishida
authors.affiliation: Department of Cardiovascular Medicine, Saga University, Saga 849-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Node
mesh_terms: D056930:ARNTL Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008322:Mammals; D051379:Mice; D041681:NIH 3T3 Cells; D056950:Period Circadian Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D056930:ARNTL Transcription Factors; D056931:Cryptochromes; C421902:PER2 protein, human; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D056926:CLOCK Proteins