Abstract
Circadian clocks are the endogenous oscillators that regulate rhythmic physiological and behavioral changes to correspond to daily light-dark cycles. Molecular dissections have revealed that transcriptional feedback loops of the circadian clock genes drive the molecular oscillation, in which PER/CRY complexes inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer to constitute a negative feedback loop. In this study, we identified the type II protein arginine methyltransferase 5 (PRMT5) as an interacting molecule of CRY1. Although the Prmt5 gene was constitutively expressed, increased interaction of PRMT5 with CRY1 was observed when the Per1 gene was repressed both in synchronized mouse liver and NIH3T3 cells. Moreover, rhythmic recruitment of PRMT5 and CRY1 to the Per1 gene promoter was found to be associated with an increased level of histone H4R3 dimethylation and Per1 gene repression. Consistently, decreased histone H4R3 dimethylation and altered rhythmic Per1 gene expression were observed in Prmt5-depleted cells. Taken together, these findings provide an insight into the link between histone arginine methylation by PRMT5 and transcriptional regulation of the circadian Per1 gene.
Highlights
Circadian clocks are the endogenous oscillators that drive metabolic, physiological, and behavioral rhythms with an intrinsic period of approximately 24 hours [1]
Dimethylation of histone H3K9 and recruitment of HP1a to the Dbp gene promoter might be the general mechanism for CRY-mediated transcription repression [21]
Since protein arginine methyltransferase 5 (PRMT5) catalyzes the dimethylation of Arg 3 on histone H4 (H4R3me2), which is generally known as a transcription repressive mark, we investigated whether rhythmic PRMT5 recruitment to the Per1 gene promoter coincides with enrichment of dimethylated H4R3
Summary
Circadian clocks are the endogenous oscillators that drive metabolic, physiological, and behavioral rhythms with an intrinsic period of approximately 24 hours [1]. The suprachiasmatic nucleus (SCN) in the anterior hypothalamus functions as a central clock, which orchestrates peripheral clocks present in almost every tissue, even in cultured cells [2,3,4,5]. Transcriptional/ translational feedback loops underlie the mammalian circadian clocks that give rise to molecular oscillation through the action of transcriptional factors such as CLOCK/BMAL1 transcriptional activators and PER/CRY transcriptional repressors [6,7]. The resulting PER/CRY complexes translocate into the nucleus with a timed delay, and inhibit the CLOCK/BMAL1-mediated transcriptional activation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
