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GENOMICS

Mapping beads on strings

Nature Methods volume 19, pages 651–652 (2022)Cite this article

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DiMeLo-seq leverages immunotethered DNA methyltransferases with long-read sequencing to map the locations of chromatin proteins in their natural context.

The long DNA of eukaryotes is packaged into chromatin by histone octamers and DNA-binding proteins that together regulate genome function. The nucleosomes formed by histone octamers wrapped in DNA appear as beads-on-a-string in electron-microscopy imaging of chromatin1, and these particles interact with each other to structure chromatin fibers and limit the binding of proteins at regulatory sites. Although methods are available to map chromatin proteins, the ability to describe chromatin features along extended lengths of chromatin has been more limited. A fruitful strategy — first noted in 1983 (ref. 2) — has been to expose eukaryotic chromatin to bacterial DNA methyltransferases. These DNA methyltransferases covalently mark DNA, but are blocked by nucleosomes and bound proteins. DNA sequencing after methylation thus identifies the protected unmethylated footprints of chromatin proteins. In this issue of Nature Methods, Altemose et al.3 describe a method to do this for specific chromatin proteins across many kilobases of DNA.

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Fig. 1: In situ methylation by DeMiLo-seq.

References

  1. Olins, A. L. & Olins, D. E. Science 183, 330–332 (1974).

    CAS  Article  Google Scholar 

  2. Fehér, Z., Kiss, A. & Venetianer, P. Nature 302, 266–268 (1983).

    Article  Google Scholar 

  3. Altemose, N. et al. Nat. Methods https://doi.org/10.1038/s41592-022-01475-6 (2022).

    Article  PubMed  Google Scholar 

  4. van Steensel, B., Delrow, J. & Henikoff, S. Nat. Genet. 27, 304–308 (2001).

    Article  Google Scholar 

  5. Rang, F. J. et al. Mol. Cell https://doi.org/10.1016/j.molcel.2022.03.009 (2022).

    Article  PubMed  Google Scholar 

  6. Carvin, C. D., Dhasarathy, A., Friesenhahn, L. B., Jessen, W. J. & Kladde, M. P. Proc. Natl Acad. Sci. USA 100, 7743–7748 (2003).

    CAS  Article  Google Scholar 

  7. Kelly, T. K. et al. Genome Res. 22, 2497–2506 (2012).

    CAS  Article  Google Scholar 

  8. Shipony, Z. et al. Nat. Methods 17, 319–327 (2020).

    CAS  Article  Google Scholar 

  9. Stergachis, A. B., Debo, B. M., Haugen, E., Churchman, L. S. & Stamatoyannopoulos, J. A. Science 368, 1449–1454 (2020).

    CAS  Article  Google Scholar 

  10. Krebs, A. R. et al. Mol. Cell 67, 411–422 (2017).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

I thank S. Allison for comments.

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  1. Division of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Kami Ahmad

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  1. Kami Ahmad
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Correspondence to Kami Ahmad.

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Ahmad, K. Mapping beads on strings. Nat Methods 19, 651–652 (2022). https://doi.org/10.1038/s41592-022-01519-x

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