Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo

Research output: Contribution to journalJournal articleResearchpeer-review

  • Bin Fang
  • Logan J. Everett
  • Jennifer Jager
  • Erika Briggs
  • Sean M. Armour
  • Dan Feng
  • Ankur Roy
  • Gerhart-Hines, Zach
  • Zheng Sun
  • Mitchell A. Lazar

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.

Original languageEnglish
JournalCell
Volume159
Issue number5
Pages (from-to)1140-1152
Number of pages13
ISSN0092-8674
DOIs
Publication statusPublished - 20 Nov 2014

Bibliographical note

Funding Information:
We thank the Functional Genomics Core (J. Schug and K. Kaestner) and Viral Vector Core (J. Johnston and A. Sandhu) of the Penn Diabetes Research Center (P30 DK19525) for next-generation sequencing and AAV production, respectively. We also thank the Penn Microarray Core for microarray analysis. We thank Dr. Ken Zaret for critical reading of the manuscript. This work was supported by NIH grants R01 DK45586 (M.A.L.), F32 DK095526 (L.J.E.), K99 DK099443 (Z.S.), and F32 DK095563 (Z.G.H.), and the JPB Foundation.

Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.

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