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Cell Chem Biol. 2019 Oct 17;26(10):1436-1449.e5. doi: 10.1016/j.chembiol.2019.08.002. Epub 2019 Aug 22.

Neutralization of the Positive Charges on Histone Tails by RNA Promotes an Open Chromatin Structure.

Author information

1
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
2
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
3
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden; Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. Electronic address: marianne.farnebo@ki.se.

Abstract

RNA associates extensively with chromatin and can influence its structure; however, the potential role of the negative charges of RNA on chromatin structure remains unknown. Here, we demonstrate that RNA prevents precipitation of histones and can attenuate electrostatic interactions between histones and DNA, thereby loosening up the chromatin structure. This effect is independent of the sequence of RNA but dependent on its single-stranded nature, length, concentration, and negative charge. Opening and closure of chromatin by RNA occurs rapidly (within minutes) and passively (in permeabilized cells), in agreement with electrostatics. Accordingly, chromatin compaction following removal of RNA can be prevented by high ionic strength or neutralization of the positively charged histone tails by hyperacetylation. Finally, LINE1 repeat RNAs bind histone H2B and can decondense chromatin. We propose that RNA regulates chromatin opening and closure by neutralizing the positively charged tails of histones, reducing their electrostatic interactions with DNA.

KEYWORDS:

LINE1 repeat; RNA; chaperone; charge-mechanism; chromatin structure; electrostatic interactions; histone tails; negative charge; neutralization; precipitation

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