Highly structured homolog pairing reflects functional organization of the Drosophila genome

Jumana AlHaj Abed, Jelena Erceg, Anton Goloborodko, Son C. Nguyen, Ruth B. McCole, Wren Saylor, Geoffrey Fudenberg, Bryan R. Lajoie, Job Dekker, Leonid A. Mirny () and C.-ting Wu ()
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Jumana AlHaj Abed: Harvard Medical School
Jelena Erceg: Harvard Medical School
Anton Goloborodko: Massachusetts Institute of Technology (MIT)
Son C. Nguyen: Harvard Medical School
Ruth B. McCole: Harvard Medical School
Wren Saylor: Harvard Medical School
Geoffrey Fudenberg: Massachusetts Institute of Technology (MIT)
Bryan R. Lajoie: University of Massachusetts Medical School
Job Dekker: University of Massachusetts Medical School
Leonid A. Mirny: Massachusetts Institute of Technology (MIT)
C.-ting Wu: Harvard Medical School

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Trans-homolog interactions have been studied extensively in Drosophila, where homologs are paired in somatic cells and transvection is prevalent. Nevertheless, the detailed structure of pairing and its functional impact have not been thoroughly investigated. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, showing that homologs pair with varying precision genome-wide, in addition to establishing trans-homolog domains and compartments. We also elucidate the structure of pairing with unprecedented detail, observing significant variation across the genome and revealing at least two forms of pairing: tight pairing, spanning 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 implication genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing, including the disruption of some interaction peaks.

Date: 2019
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DOI: 10.1038/s41467-019-12208-3

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