Modulation of histone tail electrostatic potentials in nucleosome core particles by acetylation and PARylation

• 成果类型: Article
• 署名作者: Bolik-Coulon, Nicolas; Rossler, Philip; Nosella, Michael L.; Kim, Tae Hun; Kay, Lewis E.
• 署名单位: University of Toronto; University of Toronto; University of Toronto; University of Toronto; Hospital for Sick Children (SickKids); University of Colorado System; University of Colorado Boulder; University System of Ohio; Case Western Reserve University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10992
• DOI: 10.1073/pnas.2511507122
• 发表日期: 2025-07-21
• 关键词: organization; chromatin; binding

摘要

Cellular DNA is wrapped about an octamer composed of four histone proteins forming 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.