| dbo:abstract
|
- Hi-C (or standard Hi-C) is a high-throughput genomic and epigenomic technique first described in 2009 by Lieberman-Aiden et al. to capture chromatin conformation. In general, Hi-C is considered as a derivative of a series of chromosome conformation capture technologies, including but not limited to 3C (chromosome conformation capture), 4C (chromosome conformation capture-on-chip/circular chromosome conformation capture), and 5C (chromosome conformation capture carbon copy). Hi-C comprehensively detects genome-wide chromatin interactions in the cell nucleus by combining 3C and next-generation sequencing (NGS) approaches and has been considered as a qualitative leap in C-technology (chromosome conformation capture-based technologies) development and the beginning of 3D genomics. Similar to the classic 3C technique, Hi-C measures the frequency (as an average over a cell population) at which two DNA fragments physically associate in 3D space, linking chromosomal structure directly to the genomic sequence. The general procedure of Hi-C involves first crosslinking chromatin material using formaldehyde. Then, the chromatin is solubilized and fragmented, and interacting loci are re-ligated together to create a genomic library of chimeric DNA molecules. The relative abundance of these chimeras, or ligation products, is correlated to the probability that the respective chromatin fragments interact in 3D space across the cell population. While 3C focuses on the analysis of a set of predetermined genomic loci to offer “one-versus-some” investigations of the conformation of the chromosome regions of interest, Hi-C enables “all-versus-all” interaction profiling by labeling all fragmented chromatin with a biotinylated nucleotide before ligation. As a result, biotin-marked ligation junctions can be purified more efficiently by streptavidin-coated magnetic beads, and chromatin interaction data can be obtained by direct sequencing of the Hi-C library. Analyses of Hi-C data not only reveal the overall genomic structure of mammalian chromosomes, but also offer insights into the biophysical properties of chromatin as well as more specific, long-range contacts between distant genomic elements (e.g. between genes and regulatory elements). In recent years, Hi-C has found its application in a wide variety of biological fields, including cell growth and division, transcription regulation, fate determination, development, disease, and genome evolution. By combining Hi-C data with other datasets such as genome-wide maps of chromatin modifications and gene expression profiles, the functional roles of chromatin conformation in genome regulation and stability can also be delineated. (en)
|
