ABSTRACT. The roughly two meters of DNA in the human genome is intricately packaged to form the chromatin and chromosomes in each cell nucleus. In addition to its structural role, this organization has critical regulatory functions. In particular, the formation of loops in the human genome plays an essential role in regulating genes. We recently demonstrated the ability to create reliable maps of these loops, using an in situ Hi-C method for three-dimensional genome sequencing. Hi-C characterizes the three- dimensional configuration of the genome by determining the frequency of physical contact between all pairs of loci, genome-wide. The proposed center will apply Hi-C and other new technologies to characterize genomic loops, their regulation, and their functions. We will specifically examine these structures in a wide variety of ENCODE cell types. The principles deduced from our study will be applicable to any mammalian tissue type.