Epigenetic maintenance of topological domains in the highly rearranged gibbon genome
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Abstract
The relationship between evolutionary genome remodeling and the three-dimensional structure of the genome remain largely unexplored. Here, we use the heavily rearranged gibbon genome to examine how evolutionary chromosomal rearrangements impact genome-wide chromatin interactions, topologically associating domains (TADs), and their epigenetic landscape. We use high-resolution maps of gibbon–human breaks of synteny (BOS), apply Hi-C in gibbon, measure an array of epigenetic features, and perform cross-species comparisons. We find that gibbon rearrangements occur at TAD boundaries, independent of the parameters used to identify TADs. This overlap is supported by a remarkable genetic and epigenetic similarity between BOS and TAD boundaries, namely presence of CpG islands and SINE elements, and enrichment in CTCF and H3K4me3 binding. Cross-species comparisons reveal that regions orthologous to BOS also correspond with boundaries of large (400–600 kb) TADs in human and other mammalian species. The colocalization of rearrangement breakpoints and TAD boundaries may be due to higher chromatin fragility at these locations and/or increased selective pressure against rearrangements that disrupt TAD integrity. We also examine the small portion of BOS that did not overlap with TAD boundaries and gave rise to novel TADs in the gibbon genome. We postulate that these new TADs generally lack deleterious consequences. Last, we show that limited epigenetic homogenization occurs across breakpoints, irrespective of their time of occurrence in the gibbon lineage. Overall, our findings demonstrate remarkable conservation of chromatin interactions and epigenetic landscape in gibbons, in spite of extensive genomic shuffling.
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Many higher-order chromosomal features, including TADs, lamina-associated domains, chromatin loops, and nuclear compartments, are conserved across distantly related species.
“Many such features are conserved across distantly related species.”
From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [124]
The Abstract passage says TADs are largely conserved across species, and the Discussion reports conservation of large TADs across six mammals. The cited passages do not establish comparable conservation of lamina-associated domains, chromatin loops, or nuclear compartments, so the broader list is not fully supported. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTAD and lamina-associated domain boundaries are often conserved between species and correspond with breaks of synteny between species, implying that chromosomal inversions that break TADs are selected against.
“For example, TAD and lamina-associated domain (120) boundaries are often conserved between species and correspond with breaks of synteny between species (124–126), implying that chromosomal inversions that break TADs are selected against.”
From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [124]
Overall genome topology, including TAD organization, shows conservation across distant lineages but does degrade over macroevolutionary time.
“Preliminary studies suggest that overall genome topology, including TAD organization, shows conservation across distant lineages (124–126) but does degrade over macroevolutionary time (121, 132, 133).”
From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [124]
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Topological Approaches in Animal Comparative Genomics
Schultz, D. T., & Simakov, O. (2026) · Annual Review of Animal Biosciences · doi:10.1146/annurev-animal-030424-084541 · Cited by 1 · see citing works
- Authors
- Lazar, N. H., Nevonen, K. A., O'Connell, B., McCann, C., O'Neill, R. J., Green, R. E., Meyer, T. J., Okhovat, M., & Carbone, L.
- Affiliations
- Oregon Health & Science University (US)
- University of Connecticut (US)
- University of California, Santa Cruz (US)
- Oregon National Primate Research Center (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2018-06-18
- Volume
- 28
- Issue
- 7
- Pages
- 983-997
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC6028127
- OpenAlex
- W2808777423
- Cited by
- 107
- References
- 14
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 10 · 2023: 15 · 2022: 13 · 2021: 9 · 2020: 19 · 2019: 19
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Library of Medicine Biomedical Informatics Research Training Program (T15 LM007088)
- NIH
- NCRR (P51 OD011092)
- National Science Foundation (1613856)
- Knight Cardiovascular Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- topologically associating domains, chromosomal rearrangements, TAD boundaries, chromatin interactions, CpG islands, SINE elements, CTCF binding, H3K4me3, 3D genome organization, cross-species comparison
- MeSH terms
- Animals, Chromatin, Humans, Genome, CpG Islands, Genomics, Synteny, Epigenesis, Genetic, Epigenomics
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