Cargando…

Epigenetic maintenance of topological domains in the highly rearranged gibbon genome

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 assoc...

Descripción completa

Detalles Bibliográficos
Autores principales: Lazar, Nathan H., Nevonen, Kimberly A., O'Connell, Brendan, McCann, Christine, O'Neill, Rachel J., Green, Richard E., Meyer, Thomas J., Okhovat, Mariam, Carbone, Lucia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028127/
https://www.ncbi.nlm.nih.gov/pubmed/29914971
http://dx.doi.org/10.1101/gr.233874.117
_version_ 1783336717891141632
author Lazar, Nathan H.
Nevonen, Kimberly A.
O'Connell, Brendan
McCann, Christine
O'Neill, Rachel J.
Green, Richard E.
Meyer, Thomas J.
Okhovat, Mariam
Carbone, Lucia
author_facet Lazar, Nathan H.
Nevonen, Kimberly A.
O'Connell, Brendan
McCann, Christine
O'Neill, Rachel J.
Green, Richard E.
Meyer, Thomas J.
Okhovat, Mariam
Carbone, Lucia
author_sort Lazar, Nathan H.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6028127
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-60281272019-01-01 Epigenetic maintenance of topological domains in the highly rearranged gibbon genome Lazar, Nathan H. Nevonen, Kimberly A. O'Connell, Brendan McCann, Christine O'Neill, Rachel J. Green, Richard E. Meyer, Thomas J. Okhovat, Mariam Carbone, Lucia Genome Res Research 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. Cold Spring Harbor Laboratory Press 2018-07 /pmc/articles/PMC6028127/ /pubmed/29914971 http://dx.doi.org/10.1101/gr.233874.117 Text en © 2018 Lazar et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ 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/.
spellingShingle Research
Lazar, Nathan H.
Nevonen, Kimberly A.
O'Connell, Brendan
McCann, Christine
O'Neill, Rachel J.
Green, Richard E.
Meyer, Thomas J.
Okhovat, Mariam
Carbone, Lucia
Epigenetic maintenance of topological domains in the highly rearranged gibbon genome
title Epigenetic maintenance of topological domains in the highly rearranged gibbon genome
title_full Epigenetic maintenance of topological domains in the highly rearranged gibbon genome
title_fullStr Epigenetic maintenance of topological domains in the highly rearranged gibbon genome
title_full_unstemmed Epigenetic maintenance of topological domains in the highly rearranged gibbon genome
title_short Epigenetic maintenance of topological domains in the highly rearranged gibbon genome
title_sort epigenetic maintenance of topological domains in the highly rearranged gibbon genome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028127/
https://www.ncbi.nlm.nih.gov/pubmed/29914971
http://dx.doi.org/10.1101/gr.233874.117
work_keys_str_mv AT lazarnathanh epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome
AT nevonenkimberlya epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome
AT oconnellbrendan epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome
AT mccannchristine epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome
AT oneillrachelj epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome
AT greenricharde epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome
AT meyerthomasj epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome
AT okhovatmariam epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome
AT carbonelucia epigeneticmaintenanceoftopologicaldomainsinthehighlyrearrangedgibbongenome