by Ittai E. Eres, Kaixuan Luo, Chiaowen Joyce Hsiao, Lauren E. Blake, Yoav Gilad
A growing body of evidence supports the notion that variation in gene regulation plays a crucial role in both 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. Chromatin conformation capture technologies have enabled genome-wide quantifications of such distal 3D interactions. However, relatively little comparative research in primates has been done using such technologies. To address this gap, we used Hi-C to characterize 3D chromatin interactions in induced pluripotent stem cells (iPSCs) from humans and chimpanzees. We also used RNA-seq to collect gene expression data from the same lines. We generally observed that lower-order, pairwise 3D genomic interactions are conserved in humans and chimpanzees, but higher order genomic structures, such as topologically associating domains (TADs), are not as conserved. Inter-species differences in 3D genomic interactions are often associated with gene expression differences between the species. To provide additional functional context to our observations, we considered previously published chromatin data from human stem cells. We found that inter-species differences in 3D genomic interactions, which are also associated with gene expression differences between the species, are enriched for both active and repressive marks. Overall, our data demonstrate that, as expected, an understanding of 3D genome reorganization is key to explaining regulatory evolution.