Studies utilizing MNase digestion to determine nucleosome positioning without sequencing or array information continued into the early 2000s. With the advent of whole genome sequencing in the late 1990s and early 2000s, it became possible to compare purified DNA sequences to the eukaryotic genomes of "S. cerevisiae," "Caenorhabditis elegans," "D. melanogaster," "Arabidopsis thaliana," "Mus musculus", and "Homo sapiens." MNase digestion was first applied to genome-wide nucleosome occupancy studies in "S. cerevisiae" and "C. elegans," accompanied by analyses through microarrays to determine which DNA regions were enriched with MNase-resistant nucleosomes. MNase-based microarray analyses were often utilized at genome-wide scales for yeast and in limited genomic regions in humans to determine nucleosome positioning, which could be used as an inference for transcriptional inactivation. It was not until 2008, around the time Next-Generation sequencing was being developed, when MNase digestion was combined with high-throughput sequencing, namely Solexa/Illumina sequencing, to study nucleosomal positioning at a genome-wide scale in humans. A year later, the terms “MNase-Seq” and “MNase-ChIP”, for micrococcal nuclease digestion with chromatin immunoprecipitation, were finally coined. Since its initial application in 2008, MNase-seq has been utilized to deep sequence DNA associated with nucleosome occupancy and epigenomics across eukaryotes. As of February 2020, MNase-seq is still applied to assay accessibility in chromatin. Chromatin is dynamic and the positioning of nucleosomes on DNA changes through the activity of various transcription factors and remodeling complexes, approximately reflecting transcriptional activity at these sites. DNA wrapped around nucleosomes are generally inaccessible to transcription factors. Hence, MNase-seq can be used to indirectly determine which regions of DNA are transcriptionally inaccessible by directly determining which regions are bound to nucleosomes. In a typical MNase-seq experiment, eukaryotic cell nuclei are first isolated from a tissue of interest. Then, MNase-seq uses the endo-exonuclease micrococcal nuclease to bind and cleave protein-unbound regions of DNA of eukaryotic chromatin, first cleaving and resecting one strand, then cleaving the antiparallel strand as well.