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Mol Cell. 2012 Oct 26;48(2):277-87. doi: 10.1016/j.molcel.2012.08.012. Epub 2012 Sep 13.

Circadian Dbp transcription relies on highly dynamic BMAL1-CLOCK interaction with E boxes and requires the proteasome.

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  • 1Department of Molecular Biology, Sciences III, University of Geneva, and National Centre of Competence in Research Frontiers in Genetics, 1211 Geneva, Switzerland.

Abstract

The transcription factors BMAL1 and CLOCK drive the circadian transcription of clock and clock-controlled genes, such as Dbp. To investigate the kinetics of BMAL1 binding to target genes in real time, we generated a cell line harboring tandem arrays of Dbp repeats and monitored the binding of a fluorescent BMAL1 fusion protein to these arrays by time-lapse microscopy. BMAL1 occupancy at the Dbp locus was highly circadian and strictly dependent on CLOCK. Moreover, BMAL1-CLOCK associations with Dbp were extremely unstable and displayed stochastic, proteasome-dependent fluctuations. Proteasome inhibition prolonged the residence time of BMAL1-CLOCK but resulted in an immediate attenuation of Dbp transcription. In cells harboring a single Dbp-luciferase reporter gene copy, this silencing was shown to be caused by a decrease in both the frequencies and sizes of transcriptional bursts. Thus, BMAL1 and CLOCK may act as Kamikaze activators, in that they are rapidly degraded once bound to Dbp chromatin.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22981862
[PubMed - indexed for MEDLINE]
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