. 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.
. The formation of loops between pairs of loci in the human genome plays an essential role in regulating genes and controlling how cells function and we have demonstrated the ability to create reliable maps of looping, genome-wide, using the in situ Hi-C method for three-dimensional genome sequencing. This project will study loop formation in a wide range of cell lines, identifying the specific DNA elements responsible for forming loops in each case. The project will help us understand how genome folding enables healthy cells to respond to their environment, and how altered folding contributes to disease.
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