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
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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. Program in Systems Biology Publications. https://doi.org/10.1038/s41467-019-12211-8. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/159
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This work is licensed under a Creative Commons Attribution 4.0 License.
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