Epigenetic maintenance of topological domains in the highly rearranged gibbon genome

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.

Fine-mapping complex inversion breakpoints and investigating somatic pairing in theAnopheles gambiaespecies complex using proximity-ligation sequencing

“…We obtained samples for homokaryotypic carriers of 2Rb, 2Rbc, and 2Rd arrangements (see Methods). For each colony or arrangement, we produced Hi-C libraries for pools of 5 whole adult mosquitos or 15-25 larvae following the library preparation protocol in (Lazar et al 2018) . We sequenced each library on a fraction of a Hiseq 4000 lane and obtained 12 million read pairs on average per sample.…”

“…We then filtered the homogenate through a 40um screen and fixed nuclei with 1% formaldehyde. We produce Hi-C libraries as described in (Lazar et al 2018) , and we sequenced each library on a portion of a Hiseq 4000 lane.…”

Comparing 3D genome organization in multiple species using Phylo-HMRF

“…Another study demonstrated that evolutionary changes in TAD structure correspond with the creation or elimination of CTCF binding sites using relatively low resolution Hi-C data from rhesus macaque, dog, rabbit, and mouse (Rudan et al, 2015). More recently, TADs have been shown to have strong conservation in mammalian evolution with the TADs boundaries under potential negative selections against genome rearrangements (Lazar et al, 2018;Fudenberg and Pollard, 2019). These previous analyses pointed to the conservation and changes of 3D genome structure across different species, although a more comprehensive characterization of the detailed evolutionary patterns of 3D genome organization remains unclear.…”

3D genome evolution and reorganization in theDrosophila melanogasterspecies group

“…If TAD structure is critical for proper gene regulation, then the evolution of 3D genome organization should be highly constrained and related species should show strong conservation of TAD structures. Consistent with this prediction, a variety of studies in vertebrates have reported strong conservation of 3D genome organization using comparative Hi-C approaches [8,50,26,28] . A recent study in Drosophila reported that 3D genome architecture is conserved over 40 million years of evolution in spite of extensive chromosomal rearrangements [41].…”