RT Journal Article
SR Electronic
T1 Histone variants in archaea and the evolution of combinatorial chromatin complexity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.13.037952
DO 10.1101/2020.04.13.037952
A1 Kathryn M Stevens
A1 Jacob B Swadling
A1 Antoine Hocher
A1 Corinna Bang
A1 Simonetta Gribaldo
A1 Ruth A Schmitz
A1 Tobias Warnecke
YR 2020
UL http://biorxiv.org/content/early/2020/04/14/2020.04.13.037952.abstract
AB Nucleosomes in eukaryotes act as platforms for the dynamic integration of epigenetic information. Post-translational modifications are reversibly added or removed and core histones exchanged for paralogous variants, in concert with changing demands on transcription and genome accessibility. Histones are also common in archaea. Their role in genome regulation, however, and the capacity of individual paralogs to assemble into histone-DNA complexes with distinct properties remain poorly understood. Here, we combine structural modelling with phylogenetic analysis to shed light on archaeal histone paralogs, their evolutionary history and capacity to generate complex combinatorial chromatin states through hetero-oligomeric assembly. Focusing on the human commensal Methanosphaera stadtmanae as a model archaeal system, we show that the heteromeric complexes that can be assembled from its seven histone paralogs vary substantially in DNA binding affinity and tetramer stability, occupying a large but densely populated chromatin state space. Using molecular dynamics simulations, we go on to identify unique paralogs in M. stadtmanae and Methanobrevibacter smithii that are characterized by unstable dimer:dimer interfaces. We propose that these paralogs act as capstones that prevent stable tetramer formation and extension into longer oligomers characteristic of model archaeal histones. Importantly, we provide evidence from phylogeny and genome architecture that these capstones, as well as other paralogs in the Methanobacteriales, have been maintained for hundreds of millions of years following ancient duplication events. Taken together, our findings indicate that at least some archaeal histone paralogs have evolved to play distinct and conserved functional roles, reminiscent of eukaryotic histone variants. We conclude that combinatorially complex histone-based chromatin is not restricted to eukaryotes and likely predates their emergence.Competing Interest StatementThe authors have declared no competing interest.