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Highly Structured Homolog Pairing Reflects Functional Organization of the Drosophila Genome

By Jumana AlHaj Abed, Jelena Erceg, Anton Goloborodko, Son C. Nguyen, Ruth B. McCole, Wren Saylor, Geoff Fudenberg, Bryan R. Lajoie, Job Dekker, Leonid A. Mirny, Ting (C.-ting) Wu

Posted 17 Oct 2018
bioRxiv DOI: 10.1101/443887 (published DOI: 10.1038/s41467-019-12208-3)

Trans-homolog interactions encompass potent regulatory functions, which have been studied extensively in Drosophila, where homologs are paired in somatic cells and pairing-dependent gene regulation, or transvection, is well-documented. Nevertheless, the structure of pairing and whether its functional impact is genome-wide have eluded analysis. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, discovering that homologs pair relatively precisely genome-wide in addition to establishing trans-homolog domains and compartments. We also elucidated the structure of pairing with unprecedented detail, documenting significant variation across the genome. In particular, we characterized two forms: tight pairing, consisting of contiguous small domains, and loose pairing, consisting of single larger domains. Strikingly, active genomic regions (A-type compartments, active chromatin, expressed genes) correlated with tight pairing, suggesting that pairing has a functional role genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing.

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