A giant virus genome is densely packaged by stable nucleosomes within virions

Abstract

The two doublet histones of Marseillevirus are distantly related to the four eukaryotic core histones and wrap 121 basepairs of DNA to form remarkably similar nucleosomes. By permeabilizing Marseillevirus virions and performing genome-wide nuclease digestion, chemical cleavage and mass spectrometry assays, we find that the higher-order organization of Marseillevirus chromatin fundamentally differs from that of eukaryotes. Marseillevirus nucleosomes fully protect DNA within virions as closely abutted 121-bp DNA wrapped cores without linker DNA or phasing along genes. Likewise, we observed that a large fraction of the nucleosomes reconstituted onto multi-copy tandem repeats of a nucleosome positioning sequence are tightly packed. Dense promiscuous packing of fully wrapped nucleosomes rather than "beads-on-a-string" with genic punctuation represents a new mode of DNA packaging by histones. We suggest that doublet histones have evolved for viral genome protection and may resemble an early stage of histone differentiation leading to the eukaryotic octameric nucleosome.