Exploring the Role of ATF4 in Circadian Photic Phase Shifting

Date
2018-07-23
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Abstract
The phenotypic role of activation transcription factor 4 (ATF4) in the mammalian circadian system has yet to be characterized. Previous research has provided evidence that ATF4 may play a key role in modulating molecular circadian activity, and it has been hypothesized that it may also be important for modulating photic resetting of the clock as a repressor of CREB. The main objectives of this investigation were to characterize the circadian expression of ATF4 protein in different lighting conditions, and to examine if downregulation of ATF4 using small interfering RNA (siRNA) technology would significantly potentiate photic phase shifts. In the Syrian hamster, ATF4 appeared to have a circadian expression in a light/dark cycle, but not when animals were in constant darkness. Light sufficiently increased ATF4 protein expression 2-3hrs following light exposure suggesting light plays an important role in regulating ATF4 expression. However, downregulation of ATF4 via siATF4 did not significantly potentiate phase advances to light as hypothesized. Rather, injections of siATF4 appeared to significantly alter an animal’s phase angle of entrainment. In summary, ATF4 plays an important role in the rhythmicity of the clock as light appears to be important in driving ATF4 circadian expression and its downregulation resulted in increased phase angle. However, the function of light-induced ATF4 expression remains to be determined.
Description
Keywords
Circadian Rhythms, ATF4, Photic Phase Resetting/Shifting, siRNA, CREB
Citation
Chan, R. K. (2018). Exploring the Role of ATF4 in Circadian Photic Phase Shifting (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32693