Feedback Regulation of Transcriptional Termination by the Mammalian Circadian Clock PERIOD Complex

Abstract

The Inner Workings of a Clock Eukaryotic circadian clocks are built at least in part on transcriptional feedback loops, but the mechanisms underlying circadian feedback are poorly understood. Padmanabhan et al. (p. 599 , published online 5 July) explored the transcriptional feedback mechanism at the heart of the mammalian circadian clock. The proteins PERIOD (PER) and CRYPTOCHROME suppress transcription of their own genes. PER complexes do so in part by recruiting a histone deacetylase to promoters of clock genes. But PER is also present on DNA in a complex with Senataxin, a helicase that functions in transcriptional termination. Senataxin appears to be inhibited in the PER complex, thus inhibiting termination and further reducing the rate of transcription.