Abstract
Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.
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Debbie Maizels/Springer Nature
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Acknowledgements
R.E. is a Faculty Fellow of the Edmond J. Safra Center for Bioinformatics at Tel Aviv University. This work was supported by funds from the EEF-CEC/EU ERC-AdV and NWO (NGI 93512001/2012) programs to R.A. and from the Israel Cancer Association to R.E.
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Elkon, R., Agami, R. Characterization of noncoding regulatory DNA in the human genome. Nat Biotechnol 35, 732–746 (2017). https://doi.org/10.1038/nbt.3863
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DOI: https://doi.org/10.1038/nbt.3863
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