role of type ii protein arginine methyltransferase 5 in the regulation of circadian per1 geneii型蛋白质精氨酸甲基转移酶的作用5昼夜per1基因的调控.pdfVIP

Role of Type II Protein Arginine Methyltransferase 5 in the Regulation of Circadian Per1 Gene 1 1 1 1 1 1 Jungtae Na , Kwanghyun Lee , Hwan-Gon Kim , Jee-Yoon Shin , Wonho Na , Hayan Jeong , Jong- 1 2 1 1 Woo Lee , Sehyung Cho , Won-Sun Kim , Bong-Gun Ju * 1 Department of Life Science, Sogang University, Seoul, Korea, 2 Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea 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 regulatio