RT Journal Article SR Electronic T1 Transcriptional regulatory logic of the diurnal cycle in the mouse liver JF bioRxiv FD Cold Spring Harbor Laboratory SP 077818 DO 10.1101/077818 A1 Jonathan Aryeh Sobel A1 Irina Krier A1 Teemu Andersin A1 Sunil Raghav A1 Donatella Canella A1 Federica Gilardi A1 Alexandra Styliani Kalantzi A1 Guillaume Rey A1 Benjamin Weger A1 Frederic Gachon A1 Matteo Dal Peraro A1 Nouria Hernandez A1 Ueli Schibler A1 Bart Deplancke A1 Felix Naef YR 2016 UL http://biorxiv.org/content/early/2016/09/27/077818.abstract AB 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.