Mice used in each experiment are being reared under controlled light-dark conditions. When the light-dark cycle is 12/12 hours, the starting time of the light period is “ZT0” and the starting time of the dark period is “ZT12”. “ZT” is the abbreviation for “Zeitgeber Time”. “Zeitgeber” in German is “Time giver” in English and refers to the “agent of entrainment”.
Circadian rhythms that display an approximately 24-hour cycle are generated by the transcription and translation feedback loops of the clock gene cluster (consisting of six known core factors). BMAL1 and CLOCK, representative core factor molecules, form a heterodimer. They bind to the regulatory regions (E-box) of target genes and positively regulate their transcription. The target genes include Period (Per1 and Per2) and Cryptochrome (Cry1 and Cry2). Transcribed and translated PER and CRY proteins also form a heterodimer, translocate to the nucleus, and negatively regulate the function of the BMAL1/CLOCK complex (negative feedback loop). Expression of CCGs, which have an E-box, is regulated by BMAL1/CLOCK and results in the expression of various circadian genes . ▼The product is here
Dr. Toru Takumi at RIKEN and others reported that Chrono (Gm129) is involved in the feedback loop along with BMAL1/CLOCK. CHRONO rhythmically binds to the E-box of the Bmal1 gene and inhibits the BMAL1/CLOCK function in an HDAC-dependent manner. ▼he product is here
Ko CH, Takahashi JS. Molecular components of the mammalian circadian clock. Hum Mol Genet. 2006 Oct 15 （PMID:16987893)
Akihiro Goriki et al. A Novel Protein, CHRONO, Functions as a Core Component of the Mammalian Circadian Clock. PLOS. 2014 April 15 （PMID:24736997）
BMAL1 and CLOCK also form a second core loop, a pathway to activate transcription of the Rev-erb α, and Rorα genes. When REV-ERBα and RORα bind to ROREs in the Bmal1 gene promoter separately, Bmal1 transcription is suppressed by REV-ERBα and activated by RORα. NPAS2 (Neuronal PAS domain protein 2) is an analogue of CLOCK, binds to BMAL1, and functions similarly to CLOCK. ▼The product is here