Comparative analysis of genome-wide protein-DNA interactions across domains of life reveals unique binding patterns for hypersaline archaeal histones

Abstract

DNA-binding proteins with roles in chromatin architecture and transcriptional regulation are present in all three domains of life. Histones that package DNA and regulate gene expression in eukaryotes find their evolutionary origin in the domain of life Archaea. Previously characterised archaeal histones have a somewhat conserved functional role in nucleosome formation and DNA packaging. However, previous research has indicated that the histone-like proteins of high salt-adapted archaea, or halophiles, appear to function differently. The sole histone protein encoded by the model halophilic species Halobacterium salinarum is non-essential, is involved in direct and indirect transcriptional regulation, and does not appear to package DNA. Here we use protein-DNA binding assays, computational analysis, and quantitative phenotyping to compare DNA binding patterns across halophilic histone proteins, bacterial and archaeal TFs, NAPs, and eukaryotic histones. Like TFs, halophilic histones bind the genome too sparsely to compact the genome. However, unlike TFs, binding occurs in both coding and intergenic regions. Unlike histones, halophilic histone occupancy is not depleted at the start sites of genes, and halophilic genomes lack the dinucleotide periodicity known to facilitate histone binding. We detect unique sequence preferences for histone binding in halophiles. Together these data suggest that the non-essentiality and genome-wide binding features of halophilic histone-like proteins are conserved across halophiles; they bind DNA in ways resembling both TFs and chromatin proteins, but do not appear to play a role in forming chromatin.

The chromatin landscape of the euryarchaeonHaloferax volcanii

“…In the light of recent reports casting doubt on the nucleosomal packaging of haloarchaeal genomes [24][25][26] these observations are puzzling. Once again, the picture of chromatin accessibility revealed by ATAC-seq in Haloferax is nearly identical to that of conventional eukaryotes with nucleosomal chromatin and densely packed genomes.…”

“…The picture has become even more complicated in recent years by the suggestion that in some archaea, in particular haloarchaea, the presence of histone proteins does not necessarily mean that chromatin is packaged by them [24][25][26][27][28][29] . This tentative conclusion is based on the low abundance of the HpyA protein in Haloferax proteomics datasets 28,29 and on data suggesting that it is not necessarily involved in genome packaging but has functions analogous to a transcription factor 26 .…”