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. 2017 Aug 11;357(6351):609-612.
doi: 10.1126/science.aaj1849.

Structure of histone-based chromatin in Archaea

Francesca Mattiroli  1 , Sudipta Bhattacharyya  2 , Pamela N Dyer  1 , Alison E White  1 , Kathleen Sandman  3 , Brett W Burkhart  2 , Kyle R Byrne  2 , Thomas Lee  1 , Natalie G Ahn  1 , Thomas J Santangelo  2   4 , John N Reeve  3 , Karolin Luger  5   4   6
Affiliations

Structure of histone-based chromatin in Archaea

Francesca Mattiroli et al. Science. .

Abstract

Small basic proteins present in most Archaea share a common ancestor with the eukaryotic core histones. We report the crystal structure of an archaeal histone-DNA complex. DNA wraps around an extended polymer, formed by archaeal histone homodimers, in a quasi-continuous superhelix with the same geometry as DNA in the eukaryotic nucleosome. Substitutions of a conserved glycine at the interface of adjacent protein layers destabilize archaeal chromatin, reduce growth rate, and impair transcription regulation, confirming the biological importance of the polymeric structure. Our data establish that the histone-based mechanism of DNA compaction predates the nucleosome, illuminating the origin of the nucleosome.

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Figures

Fig. 1
Fig. 1. DNA binding is conserved between archaeal and eukaryotic histones
A) The structure of three (HMfB)2 dimers bound to an 90 bp SELEX DNA is highly similar to the B) nucleosome hexasome, shown by removing one H2A–H2B heterodimer and the histone tails from the published nucleosome structure (1AOI). The axes of symmetry in both protein assemblies are indicated (Φ). C) HFs of an (HMfB) 2 dimer and (D) (H3–H4) heterodimer shown in the same orientation with associated DNA. E) The L1L2 interface of a (HMfB)2 dimer and (F) an (H3–H4) dimer is shown with conserved interactions with DNA. G) The α1α1 interface in an (HMfB)2 dimer and (H) in an (H3–H4) dimer. Further comparisons of the structures formed by HMfB and eukaryotic histones with DNA are shown in Fig. S2. In all figures, although identical, the two HMfB monomers in an (HMfB)2 dimer are colored in cyan and magenta; H3 is blue, H4 is green, H2B is red, and H2A is yellow. Regions of core histones that are not part of the histone fold are shown in white. DNA organized by HMfB is pale yellow; nucleosomal DNA is grey.
Fig. 2
Fig. 2. Archaeal histones form a continuous superhelical ramp
A) Archaeal (HMfB)2 dimers and eukaryotic core histone heterodimers polymerize through the assembly of ‘four helix bundles’ (4HBs) involving the C-termini of α2 and α3 of the HF. While the symmetric (HMfB)2 dimers can continue to polymerize forming a protein fiber with consecutive, identical 4HB bundles (oval, and inset), the asymmetry of eukaryotic core histone dimers prevents (X) continued polymerization. B) Nine (HMfB)2 dimers are shown forming a continuous protein superhelix via 4HB interactions, with groups of three consecutive dimers shown in pink, teal and wheat. Modeling confirmed that the superhelix can also be formed by HMfA homodimers, and by HMfA+HMfB heterodimers. The arrow shows the location of the G16–G16 interaction (L1L1). C) An octamer of archaeal HFs superimposes closely with the eukaryotic histone octamer (wheat colored) in the nucleosome. Helices are shown as tubes with the archaeal histones colored magenta and cyan. D) Archaeal HMfB octamer (top panel) and eukaryotic histone octamer (bottom panel) differ in their charge distribution with a more positively charged helical ramp on the surface of the histone core (the basic histone tails are excluded for clarity). Electrostatic surfaces are calculated in the ccp4mg program and displayed from −0.5 V (red) to 0.5 V (blue). The DNA backbone is shown as a line. E) DNA (shown in space filling mode) wrapped around the HMfB superhelix shown in the same orientation as in panel B). Inset shows a close-up of the annealed 2 nt 5′ extensions. One ‘supergroove’ is indicated by two arrows. F) Superposition of 120 bp of DNA organized by four (HMfB)2 HFDs with 146 bp nucleosomal DNA, shown in three orthogonal orientations; the top two orientations are identical to the orientations shown in C). Two supergrooves (minor and major) are indicated by arrows.
Fig. 3
Fig. 3. Disturbance of layer interfaces affects chromatin structure, gene transcription and growth of T. kodakarensis
A) Growth curves of T. kodakarensis TS600 and derivative strains with the HTkA G17 substitutions indicated, in medium containing S° and following dilution into a medium lacking S° (pyruvate). Error bars show the SD from three independent experiments, each run with triplicate cultures. B) Quantitative RT-PCR of transcripts of three genes in the hydrogenase operon (TK2080-TK2081-TK2088) present in T. kodakarensis cells containing HTkA or HTkA G17L grown in the presence or absence of S°. Transcripts of TK0895, TK1431 and TK1311 were quantified as constitutively expressed reference genes. Shown is the fold change of the hydrogenase transcripts in cells following dilution into a medium lacking S° (pyruvate). C) DNA fragments generated by MNase digestion of chromatin isolated from T. kodakarensis TS600 and derivative TS620 (G17D) and TS621 (G17L). DNA stripped from histones prior to MNase digestion is shown as a control (TS600). Size standards are in lanes M.
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