Stable Chromosome Condensation Revealed by Chromosome Conformation Capture

Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to 10-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes. [Display omitted] •Hi-C of polytene chromosomes reveals an equivalence of polytene bands with TADs•TADs are conserved between polytene and diploid cells•Fully extended and up to 10-fold compacted fibers constitute euchromatin•Up to 30-fold compacted fibers represent heterochromatin of the nuclear periphery Analysis of polytene bands, which are shown to correspond to topologically associating domains in interphase nuclei, reveals two stable forms of folded chromatin within euchromatic regions of diploid cells that are distinct from more highly structured heterochromatin.