Unbiased identification of regulatory region-target gene pairs in human adipocytes

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The human genome contains a vast number of putative regulatory elements and physiological trait linked haplotypes; the majority of which lie within non-coding regions and contain several association signals and genetic variants. Prediction of cell type-specific functional regulatory elements and their target genes within trait linked haplotypes is a major challenge. This complexity of regulatory region-gene pairs is driven by cell specific biochemical compatibility and/or 3D genome organisation. Focussed cell type-specific functional studies for validating target genes of selected regulatory regions have been limited and often lack scale. What is needed are highthroughput experimental manipulations of regulatory regions, combined with genome architecture mapping (GAM)3, in specific cell-types to map out important region/gene interactions and understand the contribution of 3D chromatin organisation. Human white adipose tissue (WAT) is a highly dynamic metabolic/endocrine organ functioning as an energy buffer in response to nutritional, metabolic, and environmental cues. Adipocytes (ADs), arising from adipose progenitors (APs), are the major constituent of WAT and their proportion and function are strongly associated with glycaemic, lipid, and anthropometric traits. Investigation of the genetic circuitry regulating this AD plasticity (i.e., cell fate and function) is required to further our understanding of human adipocyte biology and its role in systemic metabolism. However, current high throughput approaches often lack specificity whilst approaches focussed on specific loci lack scale.