Regulation of Pol II Pausing during Daily Gene Transcription in Mouse Liver

Abstract

Cell autonomous circadian oscillation is present in central and various peripheral tissues. The intrinsic tissue clock and various extrinsic cues drive gene expression rhythms. Transcription regulation is thought to be the main driving force for gene rhythms. However, how transcription rhythms arise remains to be fully characterized due to the fact that transcription is regulated at multiple steps. In particular, Pol II recruitment, pause release, and premature transcription termination are critical regulatory steps that determine the status of Pol II pausing and transcription output near the transcription start site (TSS) of the promoter. Recently, we showed that Pol II pausing exhibits genome-wide changes during daily transcription in mouse liver. In this article, we review historical as well as recent findings on the regulation of transcription rhythms by the circadian clock and other transcription factors, and the potential limitations of those results in explaining rhythmic transcription at the TSS. We then discuss our results on the genome-wide characteristics of daily changes in Pol II pausing, the possible regulatory mechanisms involved, and their relevance to future research on circadian transcription regulation.