Highly Structured Homolog Pairing Reflects Functional Organization of the Drosophila Genome
Jumana AlHaj Abed,
Son C. Nguyen,
Ruth B. McCole,
Bryan R. Lajoie,
Leonid A. Mirny,
Ting (C.-ting) Wu
Posted 17 Oct 2018
bioRxiv DOI: 10.1101/443887 (published DOI: 10.1038/s41467-019-12208-3)
Posted 17 Oct 2018
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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