All cells employ architectural proteins to confine and organize their chromosomes, and to prevent the otherwise thermodynamically favored collapse of concentrated DNA into compact structures. To accomplish this, prokaryotes have evolved a variety of phylogenetically unrelated, small, basic, sequence-independent DNA-binding proteins that include histones in Euryarchaeota, and members of the HU family in many Bacteria. In contrast, virtually, all Eukarya employ histones, and recently a metabolism-based hypothesis proposed that the eukaryal nucleus originated from a hydrogen-consuming, histone-containing Archaeon. Histones may have prevailed during the evolution of the Eukarya because of their extended interactions with DNA and, as noted, the histone fold now exists not only in histones but also as a structural motif in eukaryal transcription factors.