Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
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Journal | Cell |
Volume | 159 |
Issue number | 5 |
Pages (from-to) | 1140-1152 |
Number of pages | 13 |
ISSN | 0092-8674 |
DOIs | |
Publication status | Published - 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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