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. 2021 Mar 30;12:1965. doi: 10.1038/s41467-021-22284-z

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a A conceptual view of probing one-to-many cellular nanoenvironments. Individual DNA probe for T site needs to continuously cleave any proximal probes for interested biomolecules (1, 2, 3,…N) in fixed cells. New 3′-OH ends are generated on the cleaved probes, which will be detected by DNA amplification. b Schematic workflow of probing the nanoenvironment of chromatin modifications using Cell-TALKING. The nanoenvironment of three DNA modifications (5hmC, 5hmU, and 5fU) around one histone PTM is detected here as an example.