Topic Overview:
During meiosis, accurate segregation of chromosomes into gametes is essential for the preservation of ploidy and maintenance of genomic integrity. A landmark event of meiosis is crossing over (CO)―the exchange of genetic material between maternal and paternal chromosomes. Errors during CO recombination lead to aneuploidy and are the most significant cause of miscarriage and genetic abnormalities in humans.

COs require the formation of double-strand breaks to create the substrate for strand exchange. Double-strand breaks occur in small intervals, called “hotspots,” and significant variation in hotspot usage exists between and among individuals.  This variation is thought to reflect differences in sequence identity and chromatin structure, DNA topology, and/or chromosome domain organization. Yanowitz investigates how chromatin architecture impinges on meiotic crossover control―specifically, where crossovers occur, how many should occur, and how these parameters change under different growth conditions.

Using C. elegans as a model system, Yanowitz has identified a high-motility group box (HMG) domain protein, XND-1 (X nondisjunction factor 1), which regulates CO formation by modulating the levels of histone H2A lysine 5 acetylation. This work, together with recent studies on the human Prdm9 histone methyltransferase, indicates that specific subsets of histone post-translational modifications shape the meiotic recombination landscape and reveal insights into how key proteins can promote genome evolution. This work also provides the first developmental role for a conserved, but poorly characterized, histone modification.

In addition to shaping the genomic recombination landscape, xnd-1 and another gene, him-5 (high incidence of males-5), are specifically required for double-strand break formation on the X chromosome.  These are the first known genes required for CO formation on an individual chromosome and, therefore, may help explain why chromosomes have different propensities to missegregate. Yanowitz will present further insights into XND-1 and HIM-5 function and localization.