“The Flexible Nucleosome: A Cross‐Kingdom Perspective”

Abstract

In order to maintain genomic integrity, chromosomes must be segregated faithfully. The centromere is the region of the chromosome that seeds the kinetochore and is epigenetically marked by the centromere‐specific histone H3 variant CENP‐A/CENH3. Although centromeres are functionally essential, their underlying DNA sequences and associated proteins are rapidly evolving. This is known as the centromere paradox. CENP‐A's sequence is highly diverged across species, yet its function to seed the kinetochore remains intact. One possibility is that specific structural features of CENP‐A nucleosomes are conserved across the species. Indeed, in silico, in vivo, and in vitro studies have focused on the characterization of the dynamic structural behaviors of human and yeast CENP‐A nucleosomes. This dynamic behavior is thought to be predominantly driven by its αN‐helix, loop L1, and four‐helix bundle. Recently, we developed a technique to directly assess CENP‐A structural plasticity by using single‐molecule nano‐indentation force spectroscopy. We observed that human CENP‐A nucleosomes are twice as elastic compared to canonical H3 nucleosomes. In order to determine whether this observation is unique to human CENP‐A or represents a universal feature that defines a rapidly evolving CENP‐A nucleosome, we set out to investigate the elasticity of CENP‐As derived from 17 distinct species, including those that have holocentric chromosomes, spanning the three main eukaryotic kingdoms. Here, we present a progress report on our efforts to elucidate structural features underpinning the evolution of centromeric histones and its associated chromatin, which in turn serves as a model for the study of the evolution of epigenetic systems.Support or Funding InformationIntramural Research Program of CCRThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.