Archaea: The Final Frontier of Chromatin

Abstract

The three domains of life employ various strategies to organize their genomes. Archaea utilize features similar to those found in both eukaryotic and bacterial chromatin to organize their DNA. In this review, we discuss the current state of research regarding the structure-function relationships of several archaeal chromatin proteins (histones, Alba, Cren7, and Sul7d). We address individual structures as well as inferred models for higher-order chromatin formation. Each protein introduces a unique phenotype to chromatin organization, and these structures are put into the context of in vivo and in vitro data. We close by discussing the present gaps in knowledge that are preventing further studies of the organization of archaeal chromatin, on both the organismal and domain level.

Keywords: Alba; archaea; chromatin; histones; protein DNA interactions.

Figure 1:. Groups of archaea utilize different proteins to structure their genomes.

(A) Crystal structures of the four archaeal DNA-structuring proteins summarized in this review. (B) A simplified phylogeny, based on Williams et al., showing the distribution of chromatin structure-related proteins among archaea. Although debate over the true taxonomy of Archaea is ongoing, we have placed four widely discussed branches on this tree: Asgard, TACK, Euryarcheota, and DPANN. Colored bars beside each phylum denotes the type of chromatin-organizing protein present in those species. Many archaea encode both histones and Alba, but bold text highlights taxa without identified histone or Alba sequences, as shown by gaps in the green and red bars, respectively. Cren7 and Sul7d exist only in Crenarcheota, which do not typically contain histones.

Figure 2:. Archaeal histones wrap DNA into a superhelix.

(A) The crystal structure of HMfB dimers bound to 90 bp of DNA (only 30 bp of DNA is shown with one dimer bound) shows the arching of DNA induced upon binding by histones (PDB 5T5K). The RMSD between this histone arrangement and DNA-bound eukaryotic dimers is only 1.7 Å. (B) Crystal contacts in the 5T5K structure suggests an organization for higher-order chromatin compaction, where repeated stacking of dimers wraps DNA into a nucleosome-like helical ramp. Shown from both face and side views, is a model of 4 sets of HMfB dimers wrapping 120 bps of DNA. (C) Conservation of putative histone homologs found in Archaea. Highlighted regions are residues conserved at least one standard deviation more than the mean conservation across the alignment. Black frames in the sequence identify predicted α-helical structures, based on homology with HMfB. The short loops connecting the α-helices are involved in DNA binding (see A).

Figure 3:. Alba dimers encase DNA.

(A) Crystal structure of an Alba dimer from Aeropyrum pernix K1 bound to 16 bp of DNA (PDB 3U6Y). Only the first 4 bp, shown in dark grey, were resolved in the asymmetric unit, the rest are modeled in based on adjacent asymmetric units. Inset shows important DNA binding residues. (B) A model suggested by Tanaka et al. of higher order chromatin filament induced by continuous Alba dimer binding (based on PDB 3U6Y). The inset shows model of adjacent antiparallel Alba-DNA filaments. (C) Conservation of Alba family proteins found in Archaea. Highlighted regions are residues conserved at least one standard deviation more than the mean conservation across the alignment. Secondary structural elements are projected along the residue consensus sequence on the bottom of the plot.

Figure 4:. Cren7 kinks DNA into S-shaped filaments.

(A) Crystal structure of Cren7 from S. solfataricus P2 bound to 8 bp of dsDNA (PDB 4R56). Inset highlights incalation of L28 into the DNA ladder, an interaction that has been shown to stabilize the kinking of DNA strands by ~50° by Cren7. (B) Model of chromatin induced by Cren7 based on PDB 6A2I, in which monomers of Cren7 bind DNA in a head-to-tail fashion while structuring the DNA into an S-shaped filament. (C) Conservation of Cren7 homologs found in Archaea. Highlighted regions are residues conserved at least one standard deviation more than the mean conservation across the alignment. Secondary structural elements are projected along the residue consensus sequence on the bottom of the plot.

Figure 5:. Sul7d kinks DNA.

(A) Crystal structure of the Sul7d-DNA complex showing the kinking of DNA induced by Sul7d from S. acidocaldarius (PDB 1BF4). One inset shows two important residues that intercalate in the DNA double helix in a similar manner as L28 in Cren7 to stabilize the DNA kink. The other inset shows the structure of Cren7 (orange) overlayed onto that of Sul7d (purple). (B) Solution NMR structure of S. solfataricus Sul7d bound to 12 bp of DNA showing the head to head binding mode of Sul7d on DNA. (C) Conservation of Sul7d homologs found in Archaea. Highlighted regions are residues conserved at least one standard deviation more than the mean conservation across the alignment. Secondary structural elements are projected along the residue consensus sequence on the bottom of the plot.