Epigenetic gene regulation of inter-individual variability

Abstract

Variation in immune system, marked by distinct composition of immune cell types and protein levels, has been observed between healthy individuals. However, such variation is yet to be characterized at the level of gene regulation within one homogeneous cell type. Here, I profile gene expression, chromatin accessibility, genotypes, and higher-order chromatin structure of classical human blood monocytes across 24 healthy individuals of the same ethnicity to delineate individual-specific gene regulation mechanisms. I revealed that 40% of expressed genes in monocytes exhibit individual-specific expression pattern and I hypothesized such variation is mediated by cis-regulatory elements (cRE). Therefore, I utilized high resolution Hi-C data to identify significantly interacting cRE-promoter pairs to annotate distal cRE to target genes. My analysis show that gene expression could be explained by variation in chromatin accessibility of cRE and a fraction of its activity was driven by individual genotype.