Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Bioinformatics | Computational Biology | Genetic Phenomena | Genomics | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology | Systems Biology
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.
Computational biology and bioinformatics, Epigenetics, Functional genomics, Molecular biology
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DOI of Published Version
Nat Commun. 2019 Oct 3;10(1):4485. doi: 10.1038/s41467-019-12208-3. Link to article on publisher's site
AlHaj Abed J, Erceg J, Goloborodko A, Nguyen SC, McCole RB, Saylor W, Fudenberg G, Lajoie BR, Dekker J, Mirny LA, Wu C. (2019). Highly structured homolog pairing reflects functional organization of the Drosophila genome. Systems Biology Publications. https://doi.org/10.1038/s41467-019-12208-3. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/158
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