HetY · Exploring the role of heterochromatin regulation in spermatogenesis through a Sex Ratio meiotic drive system in Drosophila

Spermatogenesis is a crucial and intricate biological process for species continuity. The sex ratio (SR) meiotic drive system, prevalent in many organisms, skews offspring sex ratios by manipulating sex chromosome inheritance during meiosis. While the underlying molecular mechanisms remain elusive, recent studies suggest that heterochromatin regulation may hold a central role in most SR systems. The HetY project aims to uncover the role of heterochromatin regulation in spermatogenesis by exploiting a natural meiotic perturbation : the Paris SR system in Drosophila simulans. This system is characterized by sister chromatid nondisjunction of Y chromosomes during meiosis II, induced by two X-linked drivers, including a malfunctioning Y-linked heterochromatin protein. We hypothesize that misregulation of Y heterochromatin is responsible for this nondisjunction. Our first objective is to identify the target(s) of the X-linked driver, using advanced CUT&Tag techniques. Some Y chromosomes resist to drive, potentially due to their intrinsic ability to evade perturbations of their heterochromatin landscape. Our second objective is to characterize those perturbations, through a comprehensive transcriptomic analysis to pinpoint extensive changes in heterochromatin landscapes. Recent findings indicate that the resistant ability of Y chromosomes correlates with their simple satellite repeat composition, and studies suggest that simple satellite expression is essential for male fertility. Our third objective is to probe the role of simple satellite RNA in chromatin organization and spermatogenesis. To this end, we will design shRNA against simple satellites identified in our previous study, assessing their influence on the sex ratio phenotype and potential induction of morphological defects during spermatogenesis. Our analyses will illuminate the interplay between heterochromatin regulation and spermatogenesis, offering new insights into these essential biological processes.