The conformation of the histone H3 tail inhibits association of the BPTF PHD finger with the nucleosome. Elife 2018 Apr 12;7
Date
04/13/2018Pubmed ID
29648537Pubmed Central ID
PMC5953545DOI
10.7554/eLife.31481Scopus ID
2-s2.0-85051927084 (requires institutional sign-in at Scopus site) 88 CitationsAbstract
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.
Author List
Morrison EA, Bowerman S, Sylvers KL, Wereszczynski J, Musselman CAAuthor
Emma A. Morrison PhD Assistant Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Binding SitesChromatin Assembly and Disassembly
DNA
Histones
Humans
Models, Molecular
Nerve Tissue Proteins
Nucleosomes
PHD Zinc Fingers
Protein Binding
Protein Conformation
Protein Domains
Transcription Factors
