Rigid Cooperation of Per1 and Per2 Proteins
Affiliations
Period circadian clock (Per) genes Per1 and Per2 have essential roles in circadian oscillation. In this study, we identified a new role of Per1-Per2 cooperation, and its mechanism, using our new experimental methods. Under constant light conditions, the period length of Per1 and Per2 knockout mice depended on the copy number ratio of Per1:Per2. We then established a light-emitting diode-based lighting system that can generate any pattern of light intensity. Under gradually changing light in the absence of phase shift with different periods, both Per1((-/-)) and Per2((-/-)) mice were entrained to a broader range of period length than wild-type mice. To analyse Per1-Per2 cooperative roles at the cell culture level, we established a Per2 knockout-rescue system, which can detect period shortening in a familial advanced sleep phase syndrome (FASPS) mutant. Upon introduction of the Per1 coding region in this system, we saw period shortening. In conclusion, short period-associated protein Per1 and long period-associated Per2 cooperated to rigidly confine the circadian period to "circa" 24-h. These results suggest that the rigid circadian rhythm maintained through the cooperation of Per1-Per2 could negatively impact modern society, in which the use of artificial lighting is ubiquitous, and result in circadian disorders, including delirium.
Taufique S, Ehichioya D, Pendergast J, Yamazaki S F1000Res. 2022; 11:1018.
PMID: 36226037 PMC: 9539084. DOI: 10.12688/f1000research.125432.2.
PER2: a potential molecular marker for hematological malignancies.
Jiang H, Yang X, Mi M, Wei X, Wu H, Xin Y Mol Biol Rep. 2021; 48(11):7587-7595.
PMID: 34642831 DOI: 10.1007/s11033-021-06751-w.
Chen R, Weitzner A, McKennon L, Fonken L Brain Behav Immun Health. 2021; 17:100337.
PMID: 34589820 PMC: 8474595. DOI: 10.1016/j.bbih.2021.100337.
Binge alcohol disrupts skeletal muscle core molecular clock independent of glucocorticoids.
Tice A, Laudato J, Rossetti M, Wolff C, Esser K, Lee C Am J Physiol Endocrinol Metab. 2021; 321(5):E606-E620.
PMID: 34541876 PMC: 8791790. DOI: 10.1152/ajpendo.00187.2021.
Natural antisense transcript of regulates the amplitude of the mouse circadian clock.
Mosig R, Castaneda A, Deslauriers J, Frazier L, He K, Maghzian N Genes Dev. 2021; 35(11-12):899-913.
PMID: 34016691 PMC: 8168560. DOI: 10.1101/gad.343541.120.