RT Journal
A1 Yeung, Jake
A1 Mermet, Jérôme
A1 Jouffe, Céline
A1 Marquis, Julien
A1 Charpagne, Aline
A1 Gachon, Frédéric
A1 Naef, Felix
T1 Transcription factor activity rhythms and tissue-specific chromatin interactions explain circadian gene expression across organs
JF Genome Research 
JO Genome Research 
YR 2017 
FD December 18 
DO 10.1101/gr.222430.117 
SP gr.222430.117 
UL http://genome.cshlp.org/content/early/2017/12/15/gr.222430.117.abstract 
AB Temporal control of physiology requires the interplay between gene networks involved in daily timekeeping and tissue function across different organs. How the circadian clock interweaves with tissue-specific transcriptional programs is poorly understood. Here we dissected temporal and tissue-specific regulation at multiple gene regulatory layers by examining mouse tissues with an intact or disrupted clock over time. Integrated analysis uncovered two distinct regulatory modes underlying tissue-specific rhythms: tissue-specific oscillations in transcription factor (TF) activity, which were linked to feeding-fasting cycles in liver and sodium homeostasis in kidney; and co-localized binding of clock and tissue-specific transcription factors at distal enhancers. Chromosome conformation capture (4C-seq) in liver and kidney identified liver-specific chromatin loops that recruited clock-bound enhancers to promoters to regulate liver-specific transcriptional rhythms. Furthermore, this looping was remarkably promoter-specific on the scale of less than ten kilobases. Enhancers can contact a rhythmic promoter while looping out nearby nonrhythmic alternative promoters, confining rhythmic enhancer activity to specific promoters. These findings suggest that chromatin folding enables the clock to regulate rhythmic transcription of specific promoters to output temporal transcriptional programs tailored to different tissues.