Highly structured homolog pairing reflects functional organization of the Drosophila genome
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/125053 |
| _version_ | 1826189887902056448 |
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| author | AlHaj Abed, Jumana Erceg, Jelena Goloborodko, Anton Nguyen, Son C. McCole, Ruth B. Saylor, Wren Fudenberg, Geoffrey Lajoie, Bryan R. Dekker, Job Mirny, Leonid A. Wu, C.-ting Goloborodko |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science AlHaj Abed, Jumana Erceg, Jelena Goloborodko, Anton Nguyen, Son C. McCole, Ruth B. Saylor, Wren Fudenberg, Geoffrey Lajoie, Bryan R. Dekker, Job Mirny, Leonid A. Wu, C.-ting Goloborodko |
| author_sort | AlHaj Abed, Jumana |
| collection | MIT |
| description | 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 |
| first_indexed | 2024-09-23T08:27:34Z |
| format | Article |
| id | mit-1721.1/125053 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:27:34Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1250532022-09-30T09:21:57Z Highly structured homolog pairing reflects functional organization of the Drosophila genome AlHaj Abed, Jumana Erceg, Jelena Goloborodko, Anton Nguyen, Son C. McCole, Ruth B. Saylor, Wren Fudenberg, Geoffrey Lajoie, Bryan R. Dekker, Job Mirny, Leonid A. Wu, C.-ting Goloborodko Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Physics 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 National Institute of General Medical Sciences (U.S.) (Grant R01HD091797) National Institute of General Medical Sciences (U.S.) (Grant R01GM123289) National Institute of General Medical Sciences (U.S.) (Grant DP1GM106412) National Institute of General Medical Sciences (U.S.) (Grant R01 GM114190) 2020-05-06T15:37:48Z 2020-05-06T15:37:48Z 2019-10 2018-12 2019-10-09T17:03:43Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 https://hdl.handle.net/1721.1/125053 AlHaj Abed, Jumana et al. "Highly structured homolog pairing reflects functional organization of the Drosophila genome." Nature Communications 10 (October 2019): 4485 ©2019 The Author(s) en http://dx.doi.org/10.1038/s41467-019-12208-3 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | AlHaj Abed, Jumana Erceg, Jelena Goloborodko, Anton Nguyen, Son C. McCole, Ruth B. Saylor, Wren Fudenberg, Geoffrey Lajoie, Bryan R. Dekker, Job Mirny, Leonid A. Wu, C.-ting Goloborodko Highly structured homolog pairing reflects functional organization of the Drosophila genome |
| title | Highly structured homolog pairing reflects functional organization of the Drosophila genome |
| title_full | Highly structured homolog pairing reflects functional organization of the Drosophila genome |
| title_fullStr | Highly structured homolog pairing reflects functional organization of the Drosophila genome |
| title_full_unstemmed | Highly structured homolog pairing reflects functional organization of the Drosophila genome |
| title_short | Highly structured homolog pairing reflects functional organization of the Drosophila genome |
| title_sort | highly structured homolog pairing reflects functional organization of the drosophila genome |
| url | https://hdl.handle.net/1721.1/125053 |
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