Bintu, BogdanMateo, Leslie J.Su, Jun-HanSinnott-Armstrong, Nicholas A.Parker, MiraeKinrot, SeonYamaya, KeiBoettiger, Alistair N.Zhuang, Xiaowei2020-05-052018-10-25Bintu, Bogdan, Leslie J. Mateo, Jun-Han Su, Nicholas A. Sinnott-Armstrong, Mirae Parker, et al. "Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells." Science (2018) Oct 26; 362(6413). doi: 10.1126/science.aau1783.0036-80751095-9203http://nrs.harvard.edu/urn-3:HUL.InstRepos:42663639The spatial organization of chromatin is pivotal for regulating genome functions. We report an imaging method for tracing chromatin organization with kilobase- and nanometer-scale resolution, unveiling chromatin conformation across topologically associating domains (TADs) in thousands of individual cells. Our imaging data revealed TAD-like structures with globular conformation and sharp domain boundaries in single cells. The boundaries varied from cell to cell, occurring with non-zero probabilities at all genomic positions, but preferentially at CTCF/cohesin sites. Surprisingly, cohesin depletion, which abolished TADs at the population-average level, did not diminish domain structures in single cells, but eliminated preferential domain boundary positions. Moreover, we observed wide-spread, cooperative, multi-way chromatin interactions, which remained after cohesin depletion. These results provide critical insight into the mechanisms underlying chromatin domain and hub formation.en-USMultidisciplinaryJournal Article2020-05-0510.1126/science.aau1783