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Nat Rev Genet. 2017 Jan;18(1):51-66. doi: 10.1038/nrg.2016.138. Epub 2016 Nov 21.

From profiles to function in epigenomics.

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Institute of Stem Cell Research, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, Neuherberg 85764, Germany.
Biomedical Center, Ludwig-Maximilian University, Grosshaderner Strasse 9, Planegg-Martinsried 82152, Germany.
University College London Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK.


Myriads of epigenomic features have been comprehensively profiled in health and disease across cell types, tissues and individuals. Although current epigenomic approaches can infer function for chromatin marks through correlation, it remains challenging to establish which marks actually have causative roles in gene regulation and other processes. After revisiting how classical approaches have addressed this question in the past, we discuss the current state of epigenomic profiling and how functional information can be indirectly inferred. We also present new approaches that promise definitive functional answers, which are collectively referred to as 'epigenome editing'. In particular, we explore CRISPR-based technologies for single-locus and multi-locus manipulation. Finally, we discuss which level of function can be achieved with each approach and introduce emerging strategies for high-throughput progression from profiles to function.

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