Blood-borne circadian signal stimulates daily oscillations in actin dynamics and SRF activity

Cell. 2013 Jan 31;152(3):492-503. doi: 10.1016/j.cell.2012.12.027.


In peripheral tissues circadian gene expression can be driven either by local oscillators or by cyclic systemic cues controlled by the master clock in the brain's suprachiasmatic nucleus. In the latter case, systemic signals can activate immediate early transcription factors (IETFs) and thereby control rhythmic transcription. In order to identify IETFs induced by diurnal blood-borne signals, we developed an unbiased experimental strategy, dubbed Synthetic TAndem Repeat PROMoter (STAR-PROM) screening. This technique relies on the observation that most transcription factor binding sites exist at a relatively high frequency in random DNA sequences. Using STAR-PROM we identified serum response factor (SRF) as an IETF responding to oscillating signaling proteins present in human and rodent sera. Our data suggest that in mouse liver SRF is regulated via dramatic diurnal changes of actin dynamics, leading to the rhythmic translocation of the SRF coactivator Myocardin-related transcription factor-B (MRTF-B) into the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Active Transport, Cell Nucleus
  • Animals
  • Blood Proteins / analysis
  • Blood Proteins / metabolism
  • Cell Line
  • Cell Nucleus / metabolism
  • Circadian Rhythm*
  • Gene Expression Regulation*
  • Genetic Techniques*
  • Humans
  • Male
  • Mice
  • Period Circadian Proteins / metabolism
  • Rats
  • Serum Response Factor / metabolism*
  • Signal Transduction*
  • Transcription Factors / metabolism


  • Actins
  • Blood Proteins
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Serum Response Factor
  • Transcription Factors
  • myocardin-related transcription factor B, mouse