RNA Polymerase II Transcriptional Pausing and Release Regulates Circadian Transcription
Circadian rhythms regulate the harmonized gene expression, metabolism and physiology through transcriptional controls. It is widely accepted that the recruitment of circadian transcriptional factors has a critical role in rhythmic gene expressions. However, the roles of RNA polymerase II pausing and release (RNAP II P/R) on circadian rhythm remain largely unknown. From the massive and precise sequencing experiments, we found the static occupancies of RNAP II complex on the initiation sites and rhythmic elongation controls on Alas1 and Srebf1 genes. The subsequent genome-wide analysis retrieved 54 circadian RNAP II P/R rhythmic genes (91 transcripts) that are closely related to nutritional signals. Those genes kept unique rhythms in clock mutant mice and showed the dynamic responses under the reversed feeding regime. Here, we report a novel circadian transcription mechanism, RNAP II pausing & rhythmic release. Overall design: The 6 weeks old male mice were housed in the two light chambers with a 2hr shifted light:dark (LD)=12hrs:12hrs condition and fed ad libitum. After 4 weeks of the entrainment, a light/dark chamber was released to constant darkness (DD) condition 24hrs earlier than the other. The liver samples (N=3) were collected after 36 hours of DD condition beginning with the first point (CT00) and subsequent every 4hrs collections for each light chamber till CT44. The harvested liver samples were analyzed by ChIP-seq, PRO-seq and mRNA-seq.