Highly Structured Homolog Pairing Reflects Functional Organization of the Drosophila Genome

AlHaj Abed, J.; Erceg, J.; Goloborodko, A.; Nguyen, S. C.; McCole, R. B.; Saylor, W.; Fudenberg, G.; Lajoie, B. R.; Dekker, J.; Mirny, L. A.; Wu, T.

doi:10.1101/443887

bioRxiv · 10.1101/443887

Highly Structured Homolog Pairing Reflects Functional Organization of the Drosophila Genome

AlHaj Abed, J.·Erceg, J.·Goloborodko, A.·Nguyen, S. C.·McCole, R. B.·Saylor, W.·Fudenberg, G.·Lajoie, B. R.·Dekker, J.·Mirny, L. A.·Wu, T.

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Abstract

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.\n\nOne Sentence SummaryHaplotype-resolved Hi-C reveals structures of homolog pairing and global implications for gene activity in hybrid PnM cells.

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AlHaj Abed, J., Erceg, J., Goloborodko, A., Nguyen, S. C., McCole, R. B., Saylor, W., Fudenberg, G., Lajoie, B. R., Dekker, J., Mirny, L. A., Wu, T.. 2018-10-17. Highly Structured Homolog Pairing Reflects Functional Organization of the Drosophila Genome. https://doi.org/10.1101/443887

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