Abstract
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.
| Original language | English |
|---|---|
| Article number | 4486 |
| Pages (from-to) | 4486 |
| Journal | Nature Communications |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - 3 Oct 2019 |
| Externally published | Yes |
Bibliographical note
Funding Information:We are grateful to the Wu and Mirny laboratories, participants of the Annual Northeast Regional Chromosome Pairing Conferences, the Lieberman Aiden laboratory, 4DN DCIC, in particular Giancarlo Bonora from the Noble laboratory, Brian J. Beliveau, Guillaume J. Filion, Mirko Francesconi, Ben Lehner, M. Jordan Rowley, and the Cavalli laboratory, especially Frédéric Bantignies, for discussions, the Furlong laboratory for Oregon-R fly collection, the Rushlow laboratory for UAS-shRNA-zld line, the TUCF Genomics Sequencing Core Facility, the Microscopy Resources on North Quad (MicRoN), and the Bloomington Drosophila Stock Center for Drosophila stocks. We apologize to the authors whose work we could not cite due to constrains on referencing. This work was supported by an EMBO Long-Term Fellowship (ALTF 186-2014) to J.E., a William Randolph Hearst Award to R.B.M., and awards from NIH/NCI (Ruth L. Kirschstein NRSA, F32CA157188) to E.F.J., NIH/NHGRI (R01 HG003143) to J.D. (Howard Hughes Medical Institute investigator), NIH/NIGMS (R01 GM114190) to L.A.M., and NIH/NIGMS (RO1GM123289, DP1GM106412, R01HD091797) and HMS to C-t.W. J.D., and L.A.M. acknowledge support from the National Institutes of Health Common Fund 4D Nucleome Program (U54 DK107980).
Publisher Copyright:
© 2019, The Author(s).