Ittai Eres
University of Chicago
Interrogating the 3D Structure of the Genome in Human and Chimpanzee Tissues
Over the last several decades, a growing body of evidence has suggested that variation in gene expression plays a crucial role in both speciation and tissue differentiation. In this work, we probe regulatory divergence between humans and chimps, and across a variety of tissues, by performing Hi-C on induced pluripotent stem cells (iPSCs) from both species. Critically, these same individuals’ iPSCs are then differentiated into cells from all three definitive germ layers, allowing for a deep temporal and developmental understanding of the dynamics of 3-dimensional chromatin folding. By integrating a wide variety of orthogonal data from the same individuals (RNA-seq, methylation, ATAC-seq, etc.), we build a comprehensive picture of gene regulation and how it differs between species and between tissues. Initial analysis of Hi-C data shows that contacts are most dissimilar between humans and chimps on chromosomes with large-scale structural rearrangements between the two species (e.g. chromosomes 2, 16, and 17). The ultimate aim is to determine to what extent the variance between tissues and species seen in gene expression is concomitant with variance seen in Hi-C interaction frequency and a wide variety of other regulatory phenotypes.
Ittai Eres, Kevin Luo, Yoav Gilad
