Histones are required for packaging DNA and regulating genome function. Eukaryotic genomes encode two types of histones: canonical, like H3.2, and variant, like H3.3. Previous research has shown that tight control histone levels is required for genome function, but it is not known how relative levels of canonical and variant histones are controlled to maintain normal genome function. We hypothesized that histone chaperone proteins control the relative levels of canonical and variant histones in chromatin to ensure proper genome function. As part of a large-scale genetic screen in Drosophila melanogaster, we introduced a subset of deficiency mutations into animals with reduced canonical H3.2 and variant H3.3 gene copy number and measured viability. We identified two genes that are sensitive to changes in histone gene copy number: Polycomb, which plays a role in chromatin remodeling, and Yem, which is a variant H3.3-specific histone chaperone. We then investigated the effects of chaperone loss on viability of animals with altered H3 protein identity using genetic interaction experiments to determine if reduction in chaperone gene copy number affects viability and behavioral phenotypes. This research begins to elucidate how both the levels and types of histone H3 are modulated within the genome, including how histone chaperones play a role in this balance, therefore furthering our understanding of genome function.
Lucy Grossmann (Sat,) studied this question.