The Role of Genetic Variation on Chromatin Dynamics in Human Adipogenesis

The majority of regulatory elements and disease-associated variants are found in a large non-coding part of the human genome. Understanding the molecular principles that define interactions between these regulatory elements and distal genes remains challenging. The concept of Variable Chromatin Modules (VCMs) provides a rationale for the understanding of a high level of molecular coordination between genomic regions spanning over 100 kb and stipulate how regulatory variation shape complex traits. In this work we benchmarked different computational approaches to call VCMs using the epigenomics profiling data from human adipose stromal cells and their counterparts dierentiated adipocytes obtained from 47 individuals. We validated our approach by identifying VCMs in the know highly variable regions, such as the rhesus blood group antigen gene (RHD), HLA or the HOXA cluster. The results of this work provide a framework for further in-depth analysis of the mechanisms of genetic variation and its impact on human adipogenesis in norm and disease.