Nicolas Bolik-Coulon, Philip Rößler, Michael L. Nosella, Tae Hun Kim, Lewis E. Kay
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Modulation of histone tail electrostatic potentials in nucleosome core particles by acetylation and PARylation
Cellular DNA is wrapped about an octamer composed of four histone proteins forming the fundamental unit of chromatin structure, the nucleosome core particle (NCP). The intrinsically disordered tails of the histones serve as scaffolds for binding an array of proteins that regulate the fidelity of the genome and gene expression. A variety of posttranslational modifications (PTMs) on the tails have been characterized, including some that alter their overall charge; however, per-residue changes in tail electrostatic potentials for different PTMs have not been reported. Here, using a solution NMR approach in which enhancements of transverse relaxation rates of tail amide and methyl group protons are quantified through the addition of paramagnetic cosolutes, we examine how acetylation and PARylation modulate histone tail electrostatic potentials. Notably, even though both PTMs decrease the net positive charge carried by each tail, their electrostatic potentials either increase or decrease in a tail-specific manner relative to an unmodified NCP. A simple model of tail–DNA interactions is presented to explain these results.
期刊介绍:
The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.