UMMS Affiliation
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Publication Date
2019-10-03
Document Type
Article
Disciplines
Bioinformatics | Computational Biology | Genetic Phenomena | Genomics | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology | Systems Biology
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.
Keywords
Computational biology and bioinformatics, Epigenetics, Functional genomics, Molecular biology
Rights and Permissions
Copyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s41467-019-12208-3
Source
Nat Commun. 2019 Oct 3;10(1):4485. doi: 10.1038/s41467-019-12208-3. Link to article on publisher's site
Journal/Book/Conference Title
Nature communications
Related Resources
PubMed ID
31582763
Repository Citation
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. Program in Systems Biology Publications. https://doi.org/10.1038/s41467-019-12208-3. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/158
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Bioinformatics Commons, Computational Biology Commons, Genetic Phenomena Commons, Genomics Commons, Molecular Biology Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons, Structural Biology Commons, Systems Biology Commons