Long-range chromatin interactions in pathogenic gene expression control.

A large number of distal -regulatory elements (REs) have been annotated in the human genome, which plays a central role in orchestrating spatiotemporal gene expression. Since many REs regulate non-adjacent genes, long-range RE-promoter interactions are an important factor in the functional characterization of the engaged REs. In this regard, recent studies have demonstrated that identification of long-range target genes can decipher the effect of genetic mutations residing within REs on abnormal gene expression. In addition, investigation of altered long-range REs-promoter interactions induced by chromosomal rearrangements has revealed their critical roles in pathogenic gene expression. In this review, we briefly discuss how the analysis of 3D chromatin structure can help us understand the functional impact of REs harboring disease-associated genetic variants and how chromosomal rearrangements disrupting topologically associating domains can lead to pathogenic gene expression.