Neurobiological functions of transcriptional enhancers

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Abstract

Transcriptional enhancers are regulatory DNA elements that underlie the specificity and dynamic patterns of gene expression. Over the past decade, large-scale functional genomics projects have driven transformative progress in our understanding of enhancers. These data have relevance for identifying mechanisms of gene regulation in the CNS, elucidating the function of non-coding regulatory sequences in neurobiology and linking sequence variation within enhancers to genetic risk for neurological and psychiatric disorders. However, the sheer volume and complexity of genomic data presents a challenge to interpreting enhancer function in normal and pathogenic neurobiological processes. Here, to advance the application of genome-scale enhancer data, we offer a primer on current models of enhancer function in the CNS, we review how enhancers regulate gene expression across the neuronal lifespan, and we suggest how emerging findings regarding the role of non-coding sequence variation offer opportunities for understanding brain disorders and developing new technologies for neuroscience.

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Fig. 1: Enhancer function is dependent on sequence and context.
Fig. 2: General models of CNS regulatory wiring.
Fig. 3: Enhancers across the neuronal lifespan.
Fig. 4: How disease-associated SNPs impact enhancer function.

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Acknowledgements

This work was supported by NIH R35GM119831 (A.S.N.) and R01NS098804 (A.E.W.).

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A.S.N. and A.E.W. conceived of the review, researched the literature, wrote the manuscript and revised the manuscript.

Correspondence to Alex S. Nord or Anne E. West.

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Peer review information Nature Neuroscience thanks Erica Korb, Ian Maze, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Nord, A.S., West, A.E. Neurobiological functions of transcriptional enhancers. Nat Neurosci (2019) doi:10.1038/s41593-019-0538-5

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