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Genetic and epigenomic mechanisms of mammalian circadian transcription

Nature Structural & Molecular Biology volume 23, pages 1045–1052 (2016)Cite this article

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Abstract

The mammalian molecular clock comprises a complex network of transcriptional programs that integrates environmental signals with physiological pathways in a tissue-specific manner. Emerging technologies are extending knowledge of basic clock features by uncovering their underlying molecular mechanisms, thus setting the stage for a 'systems' view of the molecular clock. Here we discuss how recent data from genome-wide genetic and epigenetic studies have informed the understanding of clock function. In addition to its importance in human physiology and disease, the clock mechanism provides an ideal model to assess general principles of dynamic transcription regulation in vivo.

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Figure 1: The Nr1d1 gene locus.
Figure 2: Mechanisms regulating genomic binding of circadian TFs.
Figure 3: Rev-erbα and RORα coordinate rhythmic gene expression at RORE and DR2 elements.
Figure 4: Temporal view of chromatin and clock factors surrounding rhythmic E boxes.

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Acknowledgements

We thank members of the laboratory of M.A.L. for helpful discussions. Work on circadian rhythms in the lab of M.A.L. is supported by NIH R01 DK45586 and the JBP foundation, and R.P. is supported by NIH F32 DK108555.

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  1. Romeo Papazyan and Yuxiang Zhang: These authors contributed equally to this work.

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  1. Division of Endocrinology, and Metabolism; Department of Medicine; Department of Genetics; and Institute for Diabetes, Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania,

    Romeo Papazyan, Yuxiang Zhang & Mitchell A Lazar

  2. Department of Medicine, Philadelphia, Pennsylvania, USA

    Romeo Papazyan, Yuxiang Zhang & Mitchell A Lazar

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Correspondence to Yuxiang Zhang or Mitchell A Lazar.

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Papazyan, R., Zhang, Y. & Lazar, M. Genetic and epigenomic mechanisms of mammalian circadian transcription. Nat Struct Mol Biol 23, 1045–1052 (2016). https://doi.org/10.1038/nsmb.3324

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