Epigenetic maintenance of topological domains in the highly rearranged gibbon genome
- Nathan H. Lazar1,
- Kimberly A. Nevonen2,
- Brendan O'Connell3,
- Christine McCann4,5,
- Rachel J. O'Neill4,5,
- Richard E. Green3,
- Thomas J. Meyer1,
- Mariam Okhovat2 and
- Lucia Carbone1,2,6,7
- 1Bioinformatics and Computational Biology Division, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon 97239, USA;
- 2Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon 97239, USA;
- 3Department of Biomolecular Engineering, University of California, Santa Cruz, California 95064, USA;
- 4Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut 06269, USA;
- 5Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269, USA;
- 6Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97239, USA;
- 7Oregon National Primate Research Center, Beaverton, Oregon 97006, USA
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.233874.117.
- Received December 21, 2017.
- Accepted June 1, 2018.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
