Circadian Enhancers Coordinate Multiple Phases of Rhythmic Gene Transcription In Vivo

Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock.  We have determined the underlying mechanisms by measuring nascent RNA transcription around the clock in mouse liver. Unbiased examination of eRNAs that cluster in specific circadian phases identified functional enhancers driven by distinct transcription factors (TFs). We further identify on a global scale the components of the TF cistromes that function to orchestrate circadian gene expression. Integrated genomic analyses also revealed novel mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed new light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ. Nascent RNA transcripts in mouse liver were profiled at 8 time points of the 24 hour light-dark cycle. Static state mRNAs in WT and Rev-erbA -/- mice were profiled using microarray (GSE59460).