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It is well known that the chromosomes are organized in the nucleus and this spatial arrangement of genome play a crucial role in gene regulation and genome stability. Different techniques have been developed and applied to uncover the intrinsic mechanism of genome architecture, especially the chromosome conformation capture (3C) and 3C-derived methods. 3C and 3C-derived techniques provide us approaches to perform high-throughput chromatin architecture assays at the genome scale. However, the advantage and disadvantage of current methodologies of C-technologies have not been discussed extensively. In this review, we described and compared the methodologies of C-technologies used in genome organization studies with an emphasis on Hi-C method. We also discussed the crucial challenges facing current genome architecture studies based on 3C and 3C-derived technologies and the direction of future technologies to address currently outstanding questions in the field. These latest news contribute to our current understanding of genome structure, and provide a comprehensive reference for researchers to choose the appropriate method in future application. We consider that these constantly improving technologies will offer a finer and more accurate contact profiles of entire genome and ultimately reveal specific molecular machines govern its shape and function.

3C and 3C-based techniques: the powerful tools for spatial genome organization deciphering