Making the cut in the dark genome

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Science  11 Nov 2016:
Vol. 354, Issue 6313, pp. 705-706
DOI: 10.1126/science.aak9849

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Noncoding elements encompass more than 98% of the human genome and have been linked to regulatory sequences that contribute to human health and disease (1). Since the publication of the human genome sequence, considerable effort has been made to annotate functional elements, including noncoding regulatory regions—i.e., cisregulatory regions and noncoding RNAs (ncRNAs) that are involved in transcriptional regulation. Transcription factors often associate with hundreds to thousands of binding sites throughout the genome, and identifying which sites regulate gene expression often requires time-consuming and complex enhancer studies, or parallel assays in which short enhancer or promoter sequences are cloned into non-native contexts (2, 3). A recent study by Sanjana et al. (4) and a report by Fulco et al. (5) on page 769 of this issue address this obstacle using clustered regularly interspaced short palindromic repeats (CRISPR) screens to functionally characterize noncoding elements in their native context.