TY - JOUR T1 - Transcriptional regulatory logic of the diurnal cycle in the mouse liver JF - bioRxiv DO - 10.1101/077818 SP - 077818 AU - Jonathan Aryeh Sobel AU - Irina Krier AU - Teemu Andersin AU - Sunil Raghav AU - Donatella Canella AU - Federica Gilardi AU - Alexandra Styliani Kalantzi AU - Guillaume Rey AU - Benjamin Weger AU - Frederic Gachon AU - Matteo Dal Peraro AU - Nouria Hernandez AU - Ueli Schibler AU - Bart Deplancke AU - Felix Naef Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/09/27/077818.abstract N2 - Many organisms exhibit temporal rhythms in gene expression that propel diurnal cycles in physiology. In the liver of mammals, these rhythms are controlled by transcription-translation feedback loops of the core circadian clock and by feeding-fasting cycles. To better understand the regulatory interplay between the circadian clock and feeding rhythms, we mapped DNase I hypersensitive sites (DHSs) in mouse liver during a diurnal cycle. The intensity of DNase I cleavages cycled at a substantial fraction of all DHSs, suggesting that DHSs harbor regulatory elements that control rhythmic transcription. Using ChIP-seq, we found that hypersensitivity cycled in phase with RNA polymerase II (Pol II) loading and H3K27ac histone marks. We then combined the DHSs with temporal Pol II profiles in wild-type (WT) and Bmal1-/- livers to computationally identify transcription factors through which the core clock and feeding-fasting cycles control diurnal rhythms in transcription. While a similar number of mRNAs accumulated rhythmically in Bmal1-/- compared to WT livers, the amplitudes in Bmal1-/- were generally lower. The residual rhythms in Bmal1-/- reflected transcriptional regulators mediating feeding-fasting responses as well as responses to rhythmic systemic signals. Finally, the analysis of DNase I cuts at nucleotide resolution showed dynamically changing footprint consistent with dynamic binding of CLOCK:BMAL1 complexes. Structural modeling suggested that these footprints are driven by a transient hetero-tetramer binding configuration at peak activity. Together, our temporal DNase I mappings allowed us to decipher the global regulation of diurnal transcription rhythms in mouse liver. ER -