Abstract
High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their establishment remain poorly understood. Here we present high resolution Hi-C data from early Drosophila embryos. We demonstrate that boundaries between topological domains of various sizes map to DNA elements that resemble classical insulator elements: short genomic regions sensitive to DNase digestion that are strongly bound by known insulator proteins and are frequently located between divergent promoters. Further, we show a striking correspondence between these elements and the locations of mapped polytene interband regions. We believe it is likely this relationship between insulators, topological boundaries, and polytene interbands extends across the genome, and we therefore propose a model in which decompaction of boundary-insulator-interband regions drives the organization of interphase chromosomes by creating stable physical separation between adjacent domains.
Highlights
Beginning in the late 19th century, cytological investigations of the polytene chromosomes of insect salivary glands implicated the physical structure of interphase chromosomes in their cellular functions (Balbiani, 1881; Balbiani, 1890; Heitz and Bauer, 1933; King and Beams, 1934; Painter, 1935)
We propose that this relationship between insulators, topologically associated domains (TADs) and polytene interbands extends across the genome, and suggest a model in which the decompaction of these regions drives the organization of interphase fly chromosomes by creating stable physical separation between adjacent domains
The strand orientations of our reads were approximately equal in each sample, the signal decay with genomic distance was similar across samples, and, critically, visual inspection of heat maps prepared at a variety of resolutions showed these samples to be very similar both to each other and to previously published data prepared using similar methods (Sexton et al, 2012)
Summary
Beginning in the late 19th century, cytological investigations of the polytene chromosomes of insect salivary glands implicated the physical structure of interphase chromosomes in their cellular functions (Balbiani, 1881; Balbiani, 1890; Heitz and Bauer, 1933; King and Beams, 1934; Painter, 1935). Detailed examination of polytene chromosomes in Drosophila melanogaster revealed a stereotyped organization, with compacted, DNA-rich ‘bands’ alternating with extended, DNA-poor ‘interband’ regions (Bridges, 1934; Rabinowitz, 1941; Lefevre, 1976; Benyajati and Worcel, 1976; Laird and Chooi, 1976a), and it appears likely that this structure reflects general features of chromatin organization shared by non-polytene chromosomes.
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