Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Biochemistry, Biophysics, and Structural Biology | Bioinformatics | Cell Biology | Computational Biology | Developmental Biology | Embryonic Structures | Genetics | Systems Biology
Genome organization involves cis and trans chromosomal interactions, both implicated in gene regulation, development, and disease. Here, we focus on trans interactions in Drosophila, where homologous chromosomes are paired in somatic cells from embryogenesis through adulthood. We first address long-standing questions regarding the structure of embryonic homolog pairing and, to this end, develop a haplotype-resolved Hi-C approach to minimize homolog misassignment and thus robustly distinguish trans-homolog from cis contacts. This computational approach, which we call Ohm, reveals pairing to be surprisingly structured genome-wide, with trans-homolog domains, compartments, and interaction peaks, many coinciding with analogous cis features. We also find a significant genome-wide correlation between pairing, transcription during zygotic genome activation, and binding of the pioneer factor Zelda. Our findings reveal a complex, highly structured organization underlying homolog pairing, first discovered a century ago in Drosophila. Finally, we demonstrate the versatility of our haplotype-resolved approach by applying it to mammalian embryos.
Computational biology, bioinformatics, Developmental biology, Epigenetics, Genetics
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
Nat Commun. 2019 Oct 3;10(1):4486. doi: 10.1038/s41467-019-12211-8. Link to article on publisher's site
Erceg J, AlHaj Abed J, Goloborodko A, Lajoie BR, Fudenberg G, Abdennur N, Imakaev M, McCole RB, Nguyen SC, Saylor W, Joyce EF, Senaratne TN, Hannan MA, Nir G, Dekker J, Mirny LA, Wu C. (2019). The genome-wide multi-layered architecture of chromosome pairing in early Drosophila embryos. Systems Biology Publications. https://doi.org/10.1038/s41467-019-12211-8. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/159
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Biochemistry, Biophysics, and Structural Biology Commons, Bioinformatics Commons, Cell Biology Commons, Computational Biology Commons, Developmental Biology Commons, Embryonic Structures Commons, Genetics Commons, Systems Biology Commons