Active regulatory elements in eukaryotic genomes are typically associated with nucleosome-depleted regions that are hypersensitive to digestion by nonspecific endonucleases. Techniques which distinguish active regulatory elements by virtue of this include micrococcal nuclease digestion of chromatin (MNAse-seq), which preferentially depletes DNA which is not tightly bound by proteins, and formaldehyde-assisted isolation of regulatory elements (FAIRE-seq), which enriches for sequences which are nucleosome-depleted. These techniques are especially advantageous due to their limited requirements for reagents, and advances in next-generation sequencing technologies have made them increasingly useful for assessment and identification of novel regulatory elements. However, a variety of experimental and sequencing-induced biases can preclude robust detection of novel regulatory elements: variations in copy number and somy, errors in sequencing and alignment, and biases introduced by nuclease
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