Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex

Science. 2012 Aug 3;337(6094):599-602. doi: 10.1126/science.1221592. Epub 2012 Jul 5.


Eukaryotic circadian clocks are built on transcriptional feedback loops. In mammals, the PERIOD (PER) and CRYPTOCHROME (CRY) proteins accumulate, form a large nuclear complex (PER complex), and repress their own transcription. We found that mouse PER complexes included RNA helicases DDX5 and DHX9, active RNA polymerase II large subunit, Per and Cry pre-mRNAs, and SETX, a helicase that promotes transcriptional termination. During circadian negative feedback, RNA polymerase II accumulated near termination sites on Per and Cry genes but not on control genes. Recruitment of PER complexes to the elongating polymerase at Per and Cry termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. Circadian clock negative feedback thus includes direct control of transcriptional termination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Clocks / genetics*
  • Cryptochromes / genetics
  • Cryptochromes / metabolism
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Feedback, Physiological*
  • Gene Expression Regulation*
  • Mice
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • Transcription, Genetic*


  • Cryptochromes
  • Dhx9 protein, mouse
  • Per1 protein, mouse
  • Period Circadian Proteins
  • RNA Polymerase II
  • RNA polymerase II largest subunit
  • Ddx5 protein, mouse
  • DEAD-box RNA Helicases