Abstract:
Histones are a class of highly conserved DNA-binding proteins found in eukaryotes and archaea that play crucial roles in chromatin organization and gene regulation. Their evolutionary conservation and structural features make them ideal models for studying protein evolution. Histones are characterized by a core structural motif – the "histone fold" – comprising two short flanking α-helices and a long central α-helix linked by two strap loops.
In eukaryotes, histones form heterodimers that assemble into octameric complexes, wrapped by approximately 150 bp of double-stranded DNA, constituting nucleosomes – the fundamental units of chromatin. This nucleosomal structure compacts the eukaryotic genome to fit within the cell nucleus and regulates genomic DNA accessibility, contributing to transcriptional control and genome stability. In contrast, archaeal histones assemble into homo- or heterodimers that bind shorter DNA segments, forming compact and stable protein-DNA complexes. In some extremophilic archaea, histones further oligomerize into extended superhelical structures, termed hypernucleosomes, enhancing DNA protection under harsh conditions.
Although histones were previously thought to be hallmarks of eukaryotes and archaea, a recent comprehensive bioinformatic analysis identified approximately 600 histone homologs across diverse bacterial lineages. This unexpected finding suggests that histone-based DNA organization may be an evolutionary conserved feature across all domains of life. However, the structure, function, and DNA-binding mechanisms of bacterial histones remain largely unexplored. To address this knowledge gap, this study presents the structural and functional characterization of two bacterial histone candidates: HBb (Histone of Bdellovobrio bacteriovorus) and HLp (Histone of Leptospira perolatii). Using an integrative approach combining biophysical, biochemical, and computational methods, HBb has been identified as a homodimeric histone adopting the canonical histone fold. Despite its low sequence similarity to eukaryotic and archaeal histones, HBb binds DNA through a conserved interface characteristic of classical histones. Unlike nucleosomal histones, HBb induces DNA bending reminiscent of bacterial nucleoid-associated proteins such as HU, implying a role in genome compaction and dynamics in B. bacteriovorus. In contrast, HLp assembles into unconventional homotetramers – an oligomeric state not previously observed among classical histones. Nevertheless, HLp retains the fundamental DNA wrapping and compaction properties similar to its eukaryotic and archaeal counterparts, indicating a potential structural role in L. perolatii chromatin.
These findings provide compelling evidence that histone-based DNA organization extends to bacteria, challenging the long-held view that bacteria lack histones. This work offers new insights into the evolutionary history of histones and expands our understanding of chromatin organization mechanisms across all domains of life.
Histone