This detailed volume explores a variety of cutting-edge techniques used to interrogate spatial genome organization. Beginning with a section covering the vital chromosome conformation capture (3C) technique, this collection continues with chapters on targeted Hi-C approaches, sequencing-based approaches to assess nuclear environment, as well as single-cell technologies to better characterize the heterogeneity and dynamics of nuclear architectures and approaches to visualize them by microscopy. Finally, in order to be able to ask functional questions about the role of spatial chromatin organization in genomic control, the last section provides methods for acute manipulations of chromatin architecture. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.