Three-Dimensional Folding and Functional Organization Principles of the Drosophila Genome

Abstract

Chromosomes are the physical realization of genetic information and thus form the basis for its readout and propagation. Here we present a high-resolution chromosomal contact map derived from a modified genome-wide chromosome conformation capture approach applied to Drosophila embryonic nuclei. The data show that the entire genome is linearly partitioned into well-demarcated physical domains that overlap extensively with active and repressive epigenetic marks. Chromosomal contacts are hierarchically organized between domains. Global modeling of contact density and clustering of domains show that inactive domains are condensed and confined to their chromosomal territories, whereas active domains reach out of the territory to form remote intra- and interchromosomal contacts. Moreover, we systematically identify specific long-range intrachromosomal contacts between Polycomb-repressed domains. Together, these observations allow for quantitative prediction of the Drosophila chromosomal contact map, laying the foundation for detailed studies of chromosome structure and function in a genetically tractable system.

Two independent modes of chromatin organization revealed by cohesin removal

“…The co-existence of two processes with different modes and scales of action can help explain the difficulties in the field in delineating and unambiguously classifying the different features of Hi-C maps, leading to a confusing plethora of denominations and definitions 7,8,12,40–42 . Our data demonstrates clearly the existence of local, cohesin-dependent, self-interacting domains identifiable as TADs.…”

Topologically-associating domains: gene warehouses adapted to serve transcriptional regulation

“…[8][9][10][11] TADs have also been described in Drosophila. 12,13 However, in Drosophila, TADs are much smaller than in mammals. 12,13 .…”

“…12,13 However, in Drosophila, TADs are much smaller than in mammals. 12,13 . Notably, in both mammals and Drosophila, TADs are hierarchical.…”

Examining Topological Domain Influence on Enhancer Function

“…Topological domains (TADs) consist of continuous genomic regions which preferentially contact themselves more than neighbouring regions when folded in the nucleus (Dixon et al, 2012;Nora et al, 2012;Sexton et al, 2012). TAD boundaries are highly conserved between cell types, and have been proposed as a fundamental structural unit of chromatin folding (Dixon et al, 2012).…”