Poster Presentation The 44th Lorne Conference on Protein Structure and Function 2019

Tracing the origin of the nucleosome the structure of archaeal chromatin (#164)

Sudipta Bhattacharyya 1 , Francesca Mattiroli 2 , Karolin Luger 3
  1. Melbourne University, Parkville, VIC, Australia
  2. Hubrecht Institute , Utrecht, Netherlands
  3. Chemistry and Biochemistry, University of Colorado , Boulder, Colorado, USA

The nucleosome, a macromolecular complex of ~150bp of dsDNA wrapped around the central octameric histone [2X(H2A-H2B + H3-H4)] core is the fundamental building block of eukaryotic chromatin. Is the nucleosome structure a eukaryotic invention to compact increasingly larger genomic information? The question remains elusive as the basic structure of the nucleosome has remained unchanged despite of increasing genomic complexity from simple unicellular eukaryotes to complex multicellular mammals. The reminiscence of basic Nucleosome structure throughout the eukaryotic kingdom and the discovery of minimalist histones in Archaea indicate that the nucleosome predates the origin of the first eukaryote. To shed light on the evolution of nucleosome structure, we solved the crystal structure of an archaeal histone DNA complex. The structure is similar to the nucleosome with RMSD’s around 2Å when compared with yeast and human Nucleosomes. Many structural features of nucleosomal histone-DNA interactions are found to be highly preserved in archaeal chromatin . However, unlike the nucleosomal  octameric [2X(H2A-H2B + H3-H4)] histone core, archaeal chromatin consists of homo hexameric archaeal tail-less minimalist histone core [(HmfB)6] wrapped by 90bp of dsDNA molecule. In contrast to discrete Nucleosome particles, in the crystal structure, Archaeal histones form a continuous left-handed helical ramp which is wrapped by multiple 90bp dsDNA molecules, forming a semi-continuous left-handed super helix. The existence of this structure has been proved in vitro, and has been found to be pivotal for Archaeal gene regulation in vivo.  Altogether, archaeal chromatin structurere presents the ancestral version of the modern nucleosome and suggests an evolutionary path towards the eukaryotic nucleosome.