Intercalation of small molecules into DNA in chromatin is primarily controlled by superhelical constraint

Rosevalentine Bosire, Péter Nánási, László Imre, Beatrix Dienes, Árpád Szöőr, Anett Mázló, Attila Kovács, Ralf Seidel, György Vámosi, Gábor Szabó

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Abstract

The restricted access of regulatory factors to their binding sites on DNA wrapped around the nucleosomes is generally interpreted in terms of molecular shielding exerted by nucleosomal structure and internucleosomal interactions. Binding of proteins to DNA often includes intercalation of hydrophobic amino acids into the DNA. To assess the role of constrained superhelicity in limiting these interactions, we studied the binding of small molecule intercalators to chromatin in close to native conditions by laser scanning cytometry. We demonstrate that the nucleosome-constrained superhelical configuration of DNA is the main barrier to intercalation. As a result, intercalating compounds are virtually excluded from the nucleosome-occupied regions of the chromatin. Binding of intercalators to extranucleosomal regions is limited to a smaller degree, in line with the existence of net supercoiling in the regions comprising linker and nucleosome free DNA. Its relaxation by inducing as few as a single nick per ~50 kb increases intercalation in the entire chromatin loop, demonstrating the possibility for long-distance effects of regulatory potential.

Original languageEnglish
Article numbere0224936
JournalPloS one
Volume14
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Bosire, R., Nánási, P., Imre, L., Dienes, B., Szöőr, Á., Mázló, A., Kovács, A., Seidel, R., Vámosi, G., & Szabó, G. (2019). Intercalation of small molecules into DNA in chromatin is primarily controlled by superhelical constraint. PloS one, 14(11), [e0224936]. https://doi.org/10.1371/journal.pone.0224936