title: Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Fang
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Logan J
authors.initials: LJ
authors.lastname: Everett
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jager
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Briggs
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Armour
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ankur
authors.initials: A
authors.lastname: Roy
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Gerhart-Hines
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: lazar@mail.med.upenn.edu.
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D057906:Circadian Clocks; D002940:Circadian Rhythm; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C497441:Nfil3 protein, mouse; C498262:Nr1d1 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1