The Dynamic Archaeal Chromatin “Slinky”

Eukaryotic organisms package genomes that are significantly larger and more complex than genomes that are typically found in prokaryotes. The fundamental unit of compaction is the nucleosome, which is formed by histone heteromers – two H2A-H2B dimers flanking an H3-H4 tetramer – forming an octamer that binds approximately 147 bp of DNA. While histones were originally thought to only be present in eukaryotes, a plethora of histone sequences have been identified in a wide range of archaea, one of the prokaryotic domains of life. Our lab recently determined the structure of histone-based archaeal chromatin that showed striking similarities to eukaryotic nucleosomes, but crystal lattice packing and biochemical experiments suggested that archaea may form repeated stacking interactions, potentially forming long “slinky-like” extended chromatin arrangements. Here, we utilize molecular dynamics simulations, cryoEM, and analytical ultracentrifugation to study the inherent dynamics of these putative chromatin slinkies. Formation of “slinky stacking” interactions are observed to reduce system dynamics, and perturbing this interaction through stack-hindering mutations yields more flexible constructs and increases solution accessibility. The openness of the slinky is also sensitive to the salt environment. We utilize these data to explore how inherent dynamics of archaeal slinky chromatin may regulate transcription.