The conformation of the histone H3 tail inhibits association of the BPTF PHD finger with the nucleosome
- University of Iowa, United States
- Illinois Institute of Technology, United States
Abstract
Histone tails harbor a plethora of post-translational modifications that direct the function of chromatin regulators, which recognize them through effector domains. Effector domain/histone interactions have been broadly studied, but largely using peptide fragments of histone tails. Here, we extend these studies into the nucleosome context and find that the conformation adopted by the histone H3 tails is inhibitory to BPTF PHD finger binding. Using NMR spectroscopy and MD simulations, we show that the H3 tails interact robustly but dynamically with nucleosomal DNA, substantially reducing PHD finger association. Altering the electrostatics of the H3 tail via modification or mutation increases accessibility to the PHD finger, indicating that PTM crosstalk can regulate effector domain binding by altering nucleosome conformation. Together, our results demonstrate that the nucleosome context has a dramatic impact on signaling events at the histone tails, and highlights the importance of studying histone binding in the context of the nucleosome.
Article and author information
Author details
Catherine A Musselman
Funding
National Science Foundation (1452411)
- Catherine A Musselman
National Science Foundation (1552743)
- Samuel Bowerman
- Jeff Wereszczynski
Arnold and Mabel Beckman Foundation (Postdoctoral Fellowship)
- Emma A Morrison
National Institutes of Health (R35GM119647)
- Jeff Wereszczynski
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Morrison et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The conformation of the histone H3 tail inhibits association of the BPTF PHD finger with the nucleosome
eLife 7:e31481.
https://doi.org/10.7554/eLife.31481
