Circadian Dbp Transcription Relies on Highly Dynamic BMAL1-CLOCK Interaction with E Boxes and Requires the Proteasome

Sep 18, 2012Molecular cell

Daily Dbp gene activity depends on changing BMAL1-CLOCK binding to DNA and needs protein breakdown

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Abstract

BMAL1 occupancy at the Dbp locus is highly circadian and strictly dependent on CLOCK.

  • BMAL1 and CLOCK are transcription factors that regulate circadian genes.
  • Binding of BMAL1 to Dbp repeats was monitored using a fluorescent fusion protein.
  • BMAL1-CLOCK associations with Dbp are unstable and fluctuate in a stochastic manner.
  • Inhibition of the proteasome increased the binding time of BMAL1-CLOCK but decreased Dbp transcription.
  • This decrease in transcription was linked to reduced frequency and size of transcriptional bursts.

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