Unveiling the gene regulatory landscape in diseases through the identification of DNase I-hypersensitive sites

DNase I-hypersensitive sites (DHSs) serve key roles in the regulation of gene transcription as markers of cis-regulatory elements (CREs). Recent advances in next-generation sequencing have enabled the genome-wide location and annotation of DHSs in a variety of cells. Numerous studies have confirmed that DHSs are involved in several processes in cell fate decision and development. DHSs have also been indicated in cancer and inherited diseases as driver distal regulatory elements. Here, the definition of DHSs is reviewed, in addition to high-throughput methods of DHS identification. Furthermore, the function of DHSs in gene expression is probed. The roles of DHSs in disease occurrence are also reviewed and discussed. Concomitant advances in the identification of essential roles of DHSs will assist in disclosing the underlying molecular mechanisms, supplementing gene transcription and enlarging the molecular basis of DHS-related bioprocesses, phenotypes, distinct traits and diseases.