C-methods to study 3D organization of the eukaryotic genome

It is becoming increasingly evident that spatial organization of the eukaryotic genome plays an important role in regulation of gene expression. The three-dimensional (3D) genome organization can be studied using different types of microscopy, in particular those coupled with fluorescence in situ hybridization. However, when it comes to the analysis of spatial interaction between specific genome regions, much higher performance demonstrate chromosome conformation capture (3C) methods. They are based on the proximity ligation approach which consists in preferential ligation of the ends of DNA fragments joined via protein bridges in living cells by formaldehyde fixation. It is assumed that such bridges link DNA fragments that are located in close spatial proximity in the cell nucleus. In this review we describe current 3C-based approaches, from 3C and ChiP-loop to Hi-C and ChiA-PET, going under the collective name of C-methods.