Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo

Cell. 2014 Nov 20;159(5):1140-1152. doi: 10.1016/j.cell.2014.10.022.


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 enhancer RNAs (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 mechanisms by which a single circadian factor controls opposing transcriptional phases. These findings shed light on the diversity and specificity of TF function in the generation of multiple phases of circadian gene transcription in a mammalian organ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Circadian Clocks
  • Circadian Rhythm*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation*
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / genetics
  • Transcription, Genetic*


  • Basic-Leucine Zipper Transcription Factors
  • Nfil3 protein, mouse
  • Nr1d1 protein, mouse
  • Nuclear Receptor Subfamily 1, Group D, Member 1

Associated data

  • GEO/GSE59460
  • GEO/GSE59486