G34R cancer mutation alters the conformational ensemble and dynamics of the histone H3.3 tails.

ABSTRACT: In recent years, mutations in the histone variant H3.3 have been discovered in pediatric and adult gliomas and osteosarcomas. One of these is the G34R mutation in the H3.3 N-terminal tail. While this mutation is known to disrupt epigenomic pathways, the effects on nucleosome structure itself have not been explored. In light of recent studies, that have demonstrated that the interaction of the H3 tail with nucleosomal and linker DNA is driven in large part by arginine residues, we sought to determine if the G34R cancer mutation and adjacent G33R mutation, not observed in cancer, directly alter nucleosome structural dynamics. Using NMR spectroscopy and molecular dynamics simulations, we investigate the effects of these mutations on the H3 tail in the context of the nucleosome. Our results sh

SUBMITTER: Fuchs HA 

PROVIDER: S-EPMC12248080 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature