Nuclease hypersensitive sites in chromatin

Eukaryotic chromosomes participate in transcription, replication, meiotic and mitotic condensation, pairing, recombination, and segregation. These processes occur through specific interactions between nuclear proteins and chromosomal DNA sequences. Recognition of specific DNA sequences by proteins requires accessibility. In chromatin, nucleosome-free regions known as nuclease hypersensitive sites are believed to represent the 'open windows' that allow enhanced access of crucial resident cis-acting DNA sequences to trans-acting factors. These accessible regions are operationally defined by their pronounced sensitivity to nuclease cleavage or chemical modification, and are typically two orders of magnitude more sensitive than other regions in bulk chromatin. Hypersensitive sites generally represent a minor (ca. 1%), but highly selective fraction of the genome. These local regions should not be confused with long segments of the chromatin fiber extending over many kilobases (kb), associated with potentially active or actively transcribed genes, that exhibit a heightened general sensitivity to nucleases of perhaps an order of magnitude. Nuclease hypersensitive sites were first discovered in studies of SV40 viral chromatin structure in 1978, independently by Varshavsky and coworkers and by Scott & Wigmore. Their presence in cellular chromatin was first recognized by Wu & Elgin in 1979. We now know that these sites are fundamental elements in biology as they are ubiquitous among the eukaryotes, being found in the cellular chromatin of plants, animals, and fungi was well as within viral or episomal genomes.