Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells.

Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells.
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DOI:
10.1126/science.aau1783
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发表时间:
2018-10-26
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Zhuang X
Zhuang X
中科院分区:
其他
文献类型:
--
作者:
Bintu B;Mateo LJ;Su JH;Sinnott-Armstrong NA;Parker M;Kinrot S;Yamaya K;Boettiger AN;Zhuang X

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The 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 CCCTC-binding factor (CTCF)- and cohesin-binding sites. Notably, cohesin depletion, which abolished TADs at the population-average level, did not diminish domain structures in single cells, but eliminated preferential TAD-like 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.
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