Principles of Chromosome Architecture Revealed by Hi-C

Chromatin is folded by looping, self-association, and compartmentation. Many chromatin loops and TADs depend on CTCF and cohesin for their establishment and maintenance. A model of cohesin-dependent extrusion of DNA loops can explain many of the loops and TADs observed in Hi-C contact maps. Compartmentation does not depend on cohesin or CTCF. Hi-C contact maps from populations of cells reflect the superimposition of cohesin-dependent and -independent folding states. Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops. Compartmentation was not dependent on CTCF or cohesin. Hi-C contact maps represent the superimposition of CTCF/cohesin-dependent and -independent folding states. Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops. Compartmentation was not dependent on CTCF or cohesin. Hi-C contact maps represent the superimposition of CTCF/cohesin-dependent and -independent folding states. serial aligned beads or granules of chromosomes resulting from local coiling of DNA, separated from each other by interchromomeres, which are less dense. Chromomeres and interchromomeres are irregularly spaced along a chromosome. the segregation of chromatin into two compartments or at least six subcompartments that is reflected by the long-range contact pattern of off-diagonal boxes of alternating enriched or depleted contacts in Hi-C contact maps; often referred to as a ‘checkerboard’ or ‘plaid’ pattern. sets of chromosomal regions with similar, long-range Hi-C contact patterns that occur more frequently than expected based on the random polymer conformation of the chromatin fiber. a pair of loci in close physical proximity. For pairs that interact more strongly than their local neighbors, this is indicated by a radially symmetric focal peak of contact enrichment in Hi-C contact maps. giant chromosomes that result from many rounds of DNA replication without cell division while retaining pairing of homologous chromosomes and alignment of sister chromatids. This results in individual chromosomes that can easily be seen by light microscopy and display an alternating pattern of dense bands, which represent condensed chromatin, separated by less dense, loosely folded interbands; most often studied from the larval salivary glands of Drosophila melanogaster. boxes of enriched contact frequency that tile the diagonal in Hi-C contact maps; also referred to as A/B domains [67Zhang Y. et al.Spatial organization of the mouse genome and its role in recurrent chromosomal translocations.Cell. 2012; 148: 908-921Abstract Full Text Full Text PDF PubMed Scopus (409) Google Scholar], physical domains [8Sexton T. et al.Three-dimensional folding and functional organization principles of the Drosophila genome.Cell. 2012; 148: 458-472Abstract Full Text Full Text PDF PubMed Scopus (1295) Google Scholar], topological domains [6Dixon J.R. et al.Topological domains in mammalian genomes identified by analysis of chromatin interactions.Nature. 2012; 485: 376-380Crossref PubMed Scopus (3983) Google Scholar], or contact domains [5Rao S.S.P. et al.A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.Cell. 2014; 159: 1665-1680Abstract Full Text Full Text PDF PubMed Scopus (3630) Google Scholar].