The conformation of the histone H3 tail inhibits association of the BPTF PHD finger with the nucleosome

Autor: Emma A Morrison, Samuel Bowerman, Kelli L Sylvers, Jeff Wereszczynski, Catherine A Musselman
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: eLife, Vol 7 (2018)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.31481
Popis: 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.
Databáze: Directory of Open Access Journals