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Identification of circadian pathways by Synthetic TAndem Repeat PROMoter (STAR-PROM) screening

Defense Thèse de doctorat : Univ. Genève, 2012 - Sc. 4456 - 2012/07/27
Abstract 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 a novel and 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.
Keywords CircadianDiurnal actin dynamicsSRFMRTFDiurnal signaling proteinsCircadian gene expression
URN: urn:nbn:ch:unige-221497
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GERBER, Alan. Identification of circadian pathways by Synthetic TAndem Repeat PROMoter (STAR-PROM) screening. Université de Genève. Thèse, 2012. https://archive-ouverte.unige.ch/unige:22149

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Deposited on : 2012-08-15

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