Hotspot Cancer Mutation Impairs KAT8-mediated Nucleosomal Histone Acetylation

•R98W is a hotspot mutation in human cancers.•The R98W mutation impairs KAT8-mediated acetylation of nucleosomal histones.•The R98W mutation may impede accessibility of the histone tails to HAT.•The R98W mutation leads to a reduction in global H4K16 acetylation level.