GSE122520
Reorganization of 3D Genome Structure May Contribute to Gene Regulatory Evolution in Primates
A growing body of evidence supports the notion that variation in gene regulation plays a crucial role in speciation and adaptation. However, a comprehensive functional understanding of the mechanisms underlying regulatory evolution remains elusive. In primates, one of the crucial missing pieces of information towards a better understanding of regulatory evolution is a comparative annotation of interactions between distal regulatory elements and promoters. We used Hi-C to characterize 3D regulatory interactions in induced pluripotent stem cells (iPSCs) from humans and chimpanzees (Pan troglodytes). We overlaid these data with previously-collected RNA-seq data from the same cell lines. Generally, we observe that fine-scale distal 3D genomic interactions are conserved in humans and chimpanzees, but higher order genomic organization of contacts, such as TADs, are not as conserved. Inter-species differences in fine-scale 3D locus-locus interactions are often associated with gene expression differences between the species. To provide additional functional context to our observations, we also considered previously published chromatin data from human iPSCs. We found strong enrichment for both active and repressive marks in distal 3D genomic interactions that are both divergent between species and that are associated with inter-species differences in gene expression. Overall, our data demonstrates that, as expected, an understanding of 3D genome reorganization is key to explaining regulatory evolution. Overall design: Examination of Hi-C contacts in 4 individual iPSC lines from humans and 4 individual iPSC lines from chimpanzees (both sex balanced).