X chromosome inactivation in the Drosophila male germline

雌性黑腹果蝇有两条X染色体，而雄性只有一条。性别间拷贝数的差异使X染色体受到独特的进化力量和基因调控机制的影响，如剂量补偿和减数分裂性染色体失活。在本项目前期，我们发现x连锁基因的表达在雄性种系中受到抑制，但在其他组织中没有。导致这种抑制的基因和分子机制尚不清楚。为了鉴定参与这一过程的基因，我们建议对携带睾丸特异性报告基因的果蝇进行X染色体正向诱变筛选。突变基因将通过遗传作图和下一代基因组测序相结合的方法进行鉴定。这一结果将为这种染色体特异性调控过程提供首次遗传学见解。此外，我们将使用一个普遍表达的报告基因来确定x -连锁和接近剂量补偿复合物的染色体结合位点对多种组织中基因表达的影响。这将使我们能够确定剂量补偿对性别偏倚基因表达的影响，以及它如何在组织中变化。

Drosophila melanogaster females have two copies of the X chromosome, while males have only one. This difference in copy number between the sexes makes the X chromosome subject to unique evolutionary forces and gene regulatory mechanisms, such as dosage compensation and meiotic sex chromosome inactivation. In the previous phases of this project, we found that the expression of X-linked genes is suppressed in the male germline, but not in other tissues. The genes and molecular mechanisms responsible for this suppression remain unknown. To identify genes involved in this process, we propose to carry out a forward mutagenesis screen of flies carrying a testis-specific reporter gene on their X chromosome. Mutant genes will be identified using a combination of genetic mapping and next-generation genome sequencing. The results will provide the first genetic insights into this chromosome-specific regulatory process. Furthermore, we will use a ubiquitously-expressed reporter gene to determine the effects of X-linkage and proximity to a chromosomal binding site of the dosage compensation complex on gene expression in multiple tissues. This will allow us to determine the influence of dosage compensation on sex-biased gene expression and how it varies among tissues.