The DNA-binding protein HTa fromThermoplasma acidophilumis an archaeal histone analog

Histones are a principal constituent of chromatin in eukaryotes and fundamental to our understanding of eukaryotic gene regulation. In archaea, histones are phylogenetically widespread, often highly abundant, but not universal: several archaeal lineages have lost histone genes from their coding repertoire. What prompted or facilitated these losses and how archaea without histones organize their chromatin remains largely unknown. Here, we use micrococcal nuclease digestion followed by high-throughput sequencing (MNase-Seq) to elucidate primary chromatin architecture in an archaeon without histones, the acido-thermophilic archaeonThermoplasma acidophilum. We confirm and extend prior results showing thatT. acidophilumharbours a HU family protein, HTa, that is highly expressed and protects a sizeable fraction of the genome from MNase digestion. Charting HTa-based chromatin architecture across the growth cycle and comparing it to that of three histone-encoding archaea (Methanothermus fervidus, Thermococcus kodakarensisandHaloferax volcanii), we then present evidence that HTa is an archaeal histone analog. HTa-protected fragments are GC-rich, display histone-like mono- and dinucleotide patterns around a conspicuous dyad, exhibit relatively invariant positioning throughout the growth cycle, and show archaeal histone-like oligomerization dynamics. Our results suggest that HTa, a DNA-binding protein of bacterial origin, has converged onto an architectural role filled by histones in other archaea.