Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.
E-GEOD-41555 - MH003B:FOXO3 in control of circadian rhythms via direct regulation of Clock. Part 2: knockdown of FoxO3
Released on 3 June 2014, last updated on 6 June 2014
Circadian rhythms are responsive to a variety of external cues, light and metabolism being the most important. In mammals, the light signal is sensed by the retina and transmitted to the SCN master clock, where it is translated into the molecular oscillator via regulation of clock gene transcription. The signalling pathways governing the molecular translation from metabolic signals to circadian output in peripheral oscillators, in contrast, are less understood. FOXO transcription factors are known to translate external metabolic cues to internal transcriptional programs. In the past couple of years it has become evident that both FOXO transcription factors and the circadian clock are of key importance in the underlying mechanisms of ageing and the regulation of metabolism. We now show FOXO3 to be a crucial modulator of circadian rhythmicity via direct transcriptional regulation of Clock, a core component of the molecular oscillator, and identify FOXO3 as a novel link in the circadian feedback loop, which is required for circadian rhythms in liver. We propose that FOXO3 directly feeds back into the circadian oscillator in response to metabolic cues. We performed a microarray study on synchronized NIH 3T3 cells upon transient knock-down of FoxO3 (siO3). Cells were harvested for RNA isolation 24h (time1), 30h(time2), 36h(time3) and 42h(time4) after synchronization. Experimental samples were hybridized against a reference pool of cRNA, which was derived from unsynchronized NIH 3T3 cells. AS controlgroup a scrambled siRNA was transfected. Experiments were performed 4 times, of each sample group two samples were labeled with cy5 and co-hybridized with reference RNA labeled with cy3, and two samples were labeled and hybridized in the opposite way. Microarrays used were Mouse Whole Genome Gene Expression Microarrays V1 (Agilent Technologies, Belgium)
transcription profiling by array
Marian Groot Koerkamp <M.J.A.GrootKoerkamp@umcutrecht.nl>, Frank C Holstege, Gijsbertus T van der Horst, Inês Chaves, Marco F Hoekman, Marian G Koerkamp, Marten P Smidt, Raymond Schellevis, Romana M Nijman
Insulin-FOXO3 Signaling Modulates Circadian Rhythms via Regulation of Clock Transcription. Chaves I, van der Horst GT, Schellevis R, Nijman RM, Koerkamp MG, Holstege FC, Smidt MP, Hoekman MF. , PMID:24856209