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Abstract

The origin of eukaryotic chromatin represents a pivotal question in understanding the evolution of cellular complexity. Chromatin organization underpins genome accessibility, transcriptional regulation, and cellular differentiation - features that distinguish eukaryotes from their prokary- otic ancestors. Recent phylogenomic analyses identify the Asgard superphylum of archaea, including Lokiarchaeota, Heimdallarchaeota, and Hodarchaeota, among others, as the closest relatives of eukaryotes. These lineages therefore provide a unique opportunity to explore how primitive DNA-binding proteins may have evolved into the dynamic chromatin systems characteristic of eukaryotic nuclei. This doctoral research presents the first high-resolution structural and mechanistic analysis of Asgard archaeal chromatin, focusing on the core histone protein HHoB from a representative Hodarchaeal lineage. Using cryogenic electron microscopy (cryo-EM) complemented by advanced biochemical and biophysical methods, the study reveals that Asgard chromatin does not exist as a single static entity, but rather as a dynamic ensemble capable of adopting two fundamentally distinct conformations. The first, a novel open chromatin assembly, exhibits a loosely packed, filamentous architecture in which the DNA remains partially exposed, allowing potential access by transcriptional or repair machinery. The second, a closed chromatin assembly, forms a compact, highly ordered fiber stabilized by extensive inter-histone interactions. The open conformation displays structural parallels to the eukaryotic (H3–H4) octasome, and is possibly an Asgard-specific innovation toward greater chromatin flexibility. In contrast, the closed state recapitulates structural features seen in other archaeal chromatin systems, indicating evolutionary continuity across archaeal lineages. Biochemical and structural assays further reveal that divalent cations such as Mg2+ modulate the equilibrium between these states, with elevated Mg2+ concentrations favoring chromatin compaction - highlighting a possible ionic regulatory mechanism. This study provides the first structure-based model of Asgard chromatin organization, expanding our understanding of chromatin architecture in an evolutionary context.