In the beginning was the archaeosome …

Where do we come from? This is one of the essential questions to mankind and really tough to answer. The groundbreaking work of Karolin Luger and her colleagues has recently delivered the answer to a question of equal importance (at least to epigenetic researchers): Where do nucleosomes originate from? Findings reported August 2017 in Science suggest that the origins of DNA folding go back to Archaea: they use a single type of histone to wrap their DNA into a complex that very much resembles the nucleosomes of eukaryotes. It totally blew my mind when Karolin Luger presented this “Archaeosome structure” on a conference here in Munich three years ago; the superposition of their solved structure with that of the eukaryotic nucleosome (where one H2B-H2A dimer had been removed) perfectly overlapped – the whole audience was fascinated and tried to spot a difference, but there was none! On the level of the nucleosome, DNA binding seems to be conserved from Archaea to humans. In contrast, the higher-order structures found in Archaea very much differed from the ones found in eukarya. The archaeal histones form a quasi-continuous helical fiber whereas discrete particles are formed in eukaryotes and nucleosomes are separated by linker DNA. Thus, although the likely origin of histones has now been identified, another question remains (as Karolin Luger pointed out herself): how did we get from here to there?

Superposition of 5T5K and 1AOI.

Archaeal NCP (gray, 5T5K); Xenopus NCP (1A0I: H2A: yellow, H2B: red, H3: blue, H4: green). One H2A/H2B dimer of the Xenopus NCP was omitted, the N-terminal H3 tail and the C-terminal H2A and H2B tails are not shown for clarity.

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