Abstract

Eukaryotes and many archaea package their DNA with histones. While the four eukaryotic histones wrap ~147 DNA base pairs into nucleosomes, archaeal histones form 'nucleosome-like' complexes that continuously wind between 60 and 500 base pairs of DNA ('archaeasomes'), suggested by crystal contacts and analysis of cellular chromatin. Solution structures of large archaeasomes (>90 DNA base pairs) have never been directly observed. Here, we utilize molecular dynamics simulations, analytical ultracentrifugation, and cryoEM to structurally characterize the solution state of archaeasomes on longer DNA. Simulations reveal dynamics of increased accessibility without disruption of DNA-binding or tetramerization interfaces. Mg2+ concentration influences compaction, and cryoEM densities illustrate that DNA is wrapped in consecutive substates arranged 90o out-of-plane with one another. Without ATP-dependent remodelers, archaea may leverage these inherent dynamics to balance chromatin packing and accessibility.

Highlights

  • Eukaryotic genomes are orders of magnitude larger and more complex than those of archaea or bacteria

  • Archaeasomes are highly dynamic but maintain robust dimer-dimer and dimer-DNA interactions in simulations We applied molecular dynamics (MD) simulations to model the stability and solution dynamics of archaeasomes assembled on DNA of increasing lengths

  • In T. kodakarensis, the G17D (G16D in HMfB) mutation in the L1 loop was previously shown to abolish the characteristic footprint of histone-based chromatin in the cell [17], and we simulated this system at the archaeasome level (“Arc120-G17D”) to elucidate the atomistic mechanisms for this observed behavior

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Summary

Introduction

Eukaryotic genomes are orders of magnitude larger and more complex than those of archaea or bacteria. Archaeal histones share many features with their eukaryotic equivalents, such as the threehelix histone fold motif (α1-L1-α2-L2-α3) [10], as well as obligate dimerization and transient tetramer formation [11]. Histones in eukaryotes have evolved histone fold “extensions”, unique secondary structure elements that define the outer surface of the nucleosome as well as stabilize the histone core and the final turn of nucleosomal DNA. No such diversification has yet been indentified in any of the archaeal histones

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