The overall mission of this Mapping Center is to create and disseminate open access, comprehensive, high-quality, high-resolution reference maps of DNase I hypersensitive sites (DHSs) in the human and mouse genomes, at previously unattainable levels of cellular and anatomical definition. Regulatory DNA is actuated in an exceptionally state-specific manner;? accordingly, achieving a comprehensive map of DHSs necessitates the interrogation of an expansive and finely partitioned range of cell and tissue samples. Progressive technical improvementsandrecentinnovationshaveresultedindramatic(>100x)decreasesinrequisite input biological sample quantities coupled with equally dramatic (>100x) increases in assay throughput,andcorrespondingdecreasesintheincrementalcostofgeneratingreference-quality DHSmaps.Theseadvanceshaveinturnopenedthepossibilityofsystematicallyaddressingall well-defined physiologically and disease-relevant anatomic and cellular compartments. Four majorSpecificAimsaretargeted:(1)Tocreateopenaccess,comprehensivehigh-quality,high- resolutionreferencemapsofhumanDNaseIhypersensitivesites;?(2)Tocreateanddisseminate comprehensive high-quality, high-resolution reference maps of mouse DNase I hypersensitive sites;? (3) To maintain and disseminate reference indices of DNase I hypersensitive sites and footprintsinthehumanandmousegenomes;?and(4)Toenablelarge-scaleintakeofConsortium andCommunitysamplesforhigh-quality,high-throughputDHSmapping.
DNaseIhypersensitivesitesmarkthelocationsofregulatoryDNAinthegenome,andhave proventobeofremarkableutilityforunderstandingdiverseaspectsofgenomefunctionandthe geneticandmechanisticbasesofbothnormalphysiologyanddisease.Creatingdetailed, comprehensivemapsofregulatoryDNAisvitaltounlockingthepotentialofthegenometo informmedicaldecisionmaking,guidedevelopmentofnewmedicines,andimpacthuman health.
