Cryo-EM Structures of Chromatosomes Containing Human Linker Histone Variants

Abstract

Linker and core histones together condense genomic DNA by forming the chromatosome, the structural unit of metazoan chromatin. There are 11 linker histone variants in human but no high-resolution structures of chromatosomes are available. Aided by a single-chain antibody fragment, we determined the cryo-EM structures of three chromatosomes containing different linker histone variants at near atomic resolution. In these structures, the globular domains of the linker histones bind to the nucleosome dyad, but the linker DNAs displayed different conformations. We observed no well-defined densities for linker histones tails but NMR studies showed that many residues in their C-terminal tails were not observable, suggesting that the C-terminal tails likely interact with the linker DNA dynamically. Our study provides insights into the structures and dynamics of chromatosomes, which have implications for understanding the roles of different linker histone variants in chromatin structure and function.