Nucleosome composition regulates the histone H3 tail conformational ensemble and accessibility. Nucleic Acids Res 2021 May 07;49(8):4750-4767
Date
04/16/2021Pubmed ID
33856458Pubmed Central ID
PMC8096233DOI
10.1093/nar/gkab246Scopus ID
2-s2.0-85106069963 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
Hexasomes and tetrasomes are intermediates in nucleosome assembly and disassembly. Their formation is promoted by histone chaperones, ATP-dependent remodelers, and RNA polymerase II. In addition, hexasomes are maintained in transcribed genes and could be an important regulatory factor. While nucleosome composition has been shown to affect the structure and accessibility of DNA, its influence on histone tails is largely unknown. Here, we investigate the conformational dynamics of the H3 tail in the hexasome and tetrasome. Using a combination of NMR spectroscopy, MD simulations, and trypsin proteolysis, we find that the conformational ensemble of the H3 tail is regulated by nucleosome composition. As has been found for the nucleosome, the H3 tails bind robustly to DNA within the hexasome and tetrasome, but upon loss of the H2A/H2B dimer, we determined that the adjacent H3 tail has an altered conformational ensemble, increase in dynamics, and increase in accessibility. Similar to observations of DNA dynamics, this is seen to be asymmetric in the hexasome. Our results indicate that nucleosome composition has the potential to regulate chromatin signaling and ultimately help shape the chromatin landscape.
Author List
Morrison EA, Baweja L, Poirier MG, 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
ChromatinChromatin Assembly and Disassembly
DNA
Dimerization
Histones
Magnetic Resonance Spectroscopy
Mass Spectrometry
Molecular Dynamics Simulation
Nucleic Acid Conformation
Nucleosomes
Principal Component Analysis
Protein Conformation
Proteolysis
Trypsin