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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM062347-01A1
Application #
6399068
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Carter, Anthony D
Project Start
2001-07-01
Project End
2006-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
1
Fiscal Year
2001
Total Cost
$224,087
Indirect Cost
Name
University of Chicago
Department
Genetics
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637