The long-term goal of this proposal is to determine the function of a newly discovered gene family known as the CDY family in mammalian spermatogenesis. Founding members of this family are the human Y chromosomal genes CDY1 and CDY2 (together referred to as CDY). The CDY genes are linked to spermatogenic failure, as CDY1 maps to a region of the Y chromosome frequently deleted in infertile men. The role of CDY in spermatogenesis is further supported by its testis-specific expression. Other members of the CDY family are autosomal, and have expression patterns consistent with roles in both spermatogenesis and somatic development. This family of genes is shown by biochemical studies to encode a novel class of histone acetyltransferase enzymes, and are thus implicated in chromatin modification. The primary objective of this proposal is to test the hypothesis that the spermatogenic function of the CDY family is to promote chromatin condensation during spennarid maturation.
Our specific aims are: 1) To determine the precise expression profile and protein localization of this gene family during spermatogenesis. 2) To biochemically characterize the CDY family, focusing on identifying factors that engage in protein-protein interactions with members of the family, and on characterizing the enzymatic properties of these histone acetyltransferase enzymes. 3) To construct knockout and transgenic mice involving members of the CDY family, and to use these mouse models for assessing the in vivo functions of these genes. Collectively, these developmental, biochemical and genetic studies should shed light on the organismal function of the CDY family. Specifically, they will aid in evaluating the hypothetical role of this gene family in promoting chromatin condensation during spermatid maturation. Results will also have implications for understanding the molecular etiology of male infertility, and for developing drug-based male contraception.