Histone variants in archaea and the evolution of combinatorial chromatin complexity

Abstract

Nucleosomes in eukaryotes act as platforms for the dynamic integration of epigenetic information. Posttranslational 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 modeling with phylogenetic analysis to shed light on archaeal histone paralogs, their evolutionary history, and capacity to generate 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. Using molecular dynamics simulations, we go on to identify unique paralogs in M. stadtmanae and Methanobrevibacter smithii that are characterized by unstable interfaces between dimers. 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.

Extended Archaeal Histone-Based Chromatin Structure Regulates Global Gene Expression in Thermococcus kodakarensis

“…(B) A loci diagram of the annotated T. kodakarensis viral region 2 (TKVR2: TK0381-TK0421) that highlights the observed region of excision (∼TK0389 -∼TK0412) superimposed over a genome alignment plot derived from PacBio long read sequencing of TS620. (Bhattacharyya et al, 2018;Sanders et al, 2019b;Henneman et al, 2020;Stevens et al, 2020;Bowerman et al, 2021;Laursen et al, 2021).…”

“…The polymerization of histone dimers in Archaea does not resemble the nucleosome-nucleosome interactions observed in eukaryotes (Luger et al, 1997;Mattiroli et al, 2017;Sanders et al, 2019b;Henneman et al, 2020;Stevens et al, 2020;Bowerman et al, 2021). Alignments and analyses of unique archaeal histone sequences reveals the vast majority of archaeal histone proteins retain only the residues comprising the core eukaryotic histone-fold and that many amino acids are highly conserved in positions that form the histone-fold or mediate DNA interactions (Mattiroli et al, 2017;Nishida and Oshima, 2017;Zaremba-Niedzwiedzka et al, 2017;Henneman et al, 2020;Stevens et al, 2020).…”

“…While dynamic changes in AHCPs are expected, particularly in species with multiple histone isoforms (Henneman et al, 2020;Stevens et al, 2020), it is also likely that specific DNA sequences and loci are more likely to retain extended AHCPs that are important for regulating gene expression (Čuboňová et al, 2012;Nalabothula et al, 2013;Dulmage et al, 2015). Although the presence of several histone isoforms in many Archaea suggests the potential for variation in superhelix composition and length (Mattiroli et al, 2017;Bhattacharyya et al, 2018;Henneman et al, 2018;Sanders et al, 2019b;Henneman et al, 2020;Stevens et al, 2020;Bowerman et al, 2021), the viability of strains with only a single histone demonstrate that even homopolymers permit formation of AHCPs in vivo Reeve, 2001, 2006;Santangelo et al, 2009;Čuboňová et al, 2012;Dulmage et al, 2015). The biological importance of AHCPs is supported by the evolutionary retention of the AGA motif in L1 which permits close association of adjacent superhelical gyres.…”

“…Most Archaea encode histone proteins to organize their DNA into a protein:DNA complex known as chromatin ( Sandman and Reeve, 2000 , 2001 , 2006 ; Peeters et al, 2015 ; Mattiroli et al, 2017 ; Bhattacharyya et al, 2018 ; Henneman et al, 2018 ; Sanders et al, 2019b ; Henneman et al, 2020 ; Stevens et al, 2020 ; Bowerman et al, 2021 ; Laursen et al, 2021 ). The organization and tractability of chromatin structure is essential to regulate adaptive gene expression ( Wilkinson et al, 2010 ; Nalabothula et al, 2013 ; Mattiroli et al, 2017 ).…”

“…Archaeal and eukaryotic histone proteins are highly homologous, sharing conserved residues that contact DNA and retain structural elements of the histone fold ( Sandman and Reeve, 2000 ; Soares et al, 2000 ; Mattiroli et al, 2017 ). In most cases, however, the extensions or tails common to eukaryotic histones are not present in archaeal histone isoforms ( Peeters et al, 2015 ; Mattiroli et al, 2017 ; Nishida and Oshima, 2017 ; Bhattacharyya et al, 2018 ; Henneman et al, 2018 ; Henneman et al, 2020 ; Sanders et al, 2019b ; Stevens et al, 2020 ). Unlike their eukaryotic counterparts, archaeal histones can homodimerize and spontaneously oligomerize to form chromatin with a single protein ( Decanniere et al, 2000 ; Mattiroli et al, 2017 ; Bhattacharyya et al, 2018 ; Henneman et al, 2020 ; Stevens et al, 2020 ; Bowerman et al, 2021 ; Laursen et al, 2021 ), and thus unlike their eukaryotic counterparts ( Luger et al, 1997 ), archaeal chromatin structures are not defined in size.…”