Microscopy of histone-humanized yeast strains

Eukaryotic DNA wraps around well-conserved histone octamers to form nucleosome fibers, which represents the most basic functional organization of chromatin among divergent organisms. As the effects of species-specific changes on nucleosome functions remain poorly characterized, histone replacement between divergent species can help identify processes that are functionally entrenched in different organisms.
In this work we have characterized biological effects of the human-like nucleosomes, showing their direct impact on the overall structure of the chromatin in Saccharomyces cerevisiae. We used transmission electron microscopy (TEM) and found a size increase in the human nucleosome core particle (NCP), linked to shorter free linker DNA, suggesting that chromatin is less accessible. Moreover, human histones caused nucleolar fragmentation linked to rDNA array instability, through an RNA-polymerase II dependent mechanism, leading to its extraordinary, but entirely reversible, intra-chromosomal expansion.