Light-independent role of CRY1 and CRY2 in the mammalian circadian clock.
Cryptochrome (CRY), a photoreceptor for the circadian clock in Drosophila, binds to the clock component TIM in a light-dependent fashion and blocks its function. In mammals, genetic evidence suggests a role for CRYs within the clock, distinct from hypothetical photoreceptor functions. Mammalian CRY1 and CRY2 are here shown to act as light-independent inhibitors of CLOCK-BMAL1, the activator driving Per1 transcription. CRY1 or CRY2 (or both) showed light-independent interactions with CLOCK and BMAL1, as well as with PER1, PER2, and TIM. Thus, mammalian CRYs act as light-independent components of the circadian clock and probably regulate Per1 transcriptional cycling by contacting both the activator and its feedback inhibitors.
Griffin
E A
EA
Department of Neurobiology, Harvard Medical School, Boston, MA 02115 USA.
Staknis
D
D
Weitz
C J
CJ
D016475:3T3 Cells; D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002940:Circadian Rhythm; D056931:Cryptochromes; D019281:Dimerization; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008027:Light; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538961:Bmal1 protein, mouse; C538963:CRY1 protein, human; C538966:CRY2 protein, human; C538964:Cry1 protein, mouse; C538967:Cry2 protein, mouse; C539022:PER1 protein, human; C421902:PER2 protein, human; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C509769:TIMELESS protein, human; C509770:Timeless protein, mouse; C119828:cry protein, Drosophila; C538943:CLOCK protein, human; C538944:Clock protein, mouse