Novel histones and histone variant families in prokaryotes

Abstract

AbstractHistones are important chromatin-organising proteins in eukaryotes and archaea. They form superhelical structures around which DNA is wrapped. Recent studies have shown that some archaea and bacteria contain alternative histones that exhibit different DNA binding properties, in addition to highly divergent sequences. However, the vast majority of these new histones are identified in metagenomes and thus are difficult to study in vivo. The recent revolutionary breakthroughs in in silico protein structure prediction by AlphaFold2 and RoseTTAfold allow for unprecedented insights into the possible function and structure of currently unstudied proteins. Here, we categorise the complete prokaryotic histone space into 17 distinct groups based on AlphaFold predictions. We identify a new superfamily of histones, termedα3 histones, which are common in archaea and present in several bacteria. Importantly, we establish the existence of a large family of histones throughout archaea and in some bacteriophages that, instead of wrapping DNA, likely bridge DNA, therewith diverging from conventional nucleosomal histones.