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


Autoři: Rosevalentine Bosire aff001;  Péter Nánási, Jr. aff001;  László Imre aff001;  Beatrix Dienes aff003;  Árpád Szöőr aff001;  Anett Mázló aff004;  Attila Kovács aff006;  Ralf Seidel aff007;  György Vámosi aff001;  Gábor Szabó aff001
Působiště autorů: Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary aff001;  Doctoral School of Molecular Cell and Immune Biology, University of Debrecen, Debrecen, Hungary aff002;  Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary aff003;  Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary aff004;  MTA-DE Cell Biology and Signalling Research Group, University of Debrecen, Debrecen, Hungary aff005;  Department of Radiation Therapy, Faculty of Medicine, University of Debrecen, Debrecen, Hungary aff006;  Peter Debye Institute for Soft Matter Physics, University of Leipzig, Leipzig, Germany aff007
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224936

Souhrn

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.

Klíčová slova:

Cell binding – Cell staining – DNA-binding proteins – Fluorescence imaging – Histones – Chromatin – Nuclear staining – Nucleosomes


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2019 Číslo 11