Wang, S. et al. Science 353, 598–602 (2016).

Chromosome conformation capture methods such as Hi-C have been crucial for studying the structural organization of chromosomal DNA. However, these ensemble measurements may average out structural details, as they occur on the single-chromosome scale. To bypass this potential limitation, Wang et al. developed an imaging-based approach for mapping the spatial organization of chromosomes. Specifically, they mapped structures known from Hi-C data as topologically associated domains (TADs) using a combination of a modified version of the Oligopaint labeling strategy and a multiplexed in situ hybridization approach previously developed in the laboratory of Xiaowei Zhuang at Harvard University. Using this approach, they labeled known TADs on several human chromosomes, as well as active and inactive X chromosomes. Their results correlated well with many results obtained with Hi-C, including the observation of active and inactive regions within individual TADs, and allowed for complementary discoveries.