Current bioinformatic approaches to identify DNase I hypersensitive sites and genomic footprints from DNase-seq data

CHROMATIN ACCESSIBILITY The formation of regions of open chromatin or nucleosome loss in eukaryotic genomes is an important factor elucidating potential regulatory activity. Nucleosome packaging, which organizes the DNA structure, acts as a regulator of transcription by enabling or restricting protein binding, and therefore facilitating the replication and coordination of gene activity (Cockerill, 2011). In addition, chromatin accessibility, which has been determined traditionally by regions of “open” or “closed” conformation, is subjected to dynamically changing events at accessible cis-regulatory elements (Bell et al., 2011). Chromatin accessibility can be examined by DNase I digestion, and then uncovered by the DNase I cleavage pattern (Wu et al., 1979). The combination of DNase I digestion and high-throughput sequencing (DNase-seq) has been used to map chromatin accessibility in vivo in a given tissue or cell-type on a genomewide scale (Song and Crawford, 2010). This technique allows for an unprecedented increase both in resolution and the range spanned, compared to the prenext generation sequencing era (Kodama et al., 2007). The current DNase-seq protocol has been adapted from the methodology described by Boyle et al. (2008a), achieving higher resolution than DNasechip, and can be applied to any species with a sequenced genome. Although, the analysis of data coming from sequencing technologies such as chromatin immunoprecipitation followed by sequencing (ChIP-seq), or whole transcriptome shotgun sequencing (RNA-seq) have concentrated a huge level of research effort, methodologies for the analysis of DNase-seq data are relatively immature (Song and Crawford, 2010). This data presents its own peculiarities and should not be merely treated as ChIP-seq data, but instead linked to it to provide biological insights of chromatin domains and transcriptional regulation. The general view conceives regions of open chromatin spanning nucleosome-free or nucleosomedepleted regions often in the vicinity of transcription factor binding events.