Fellowship Donald Chadwick Wilkerson / Heat Shock Transcription Factors and their Role in Spermatogenesis and Early Embryogenesis

The goal of this project will be focused on understanding the role(s) of heat shock transcription factor I (HSFI) and 2 (HSF2) in spermatogenesis and early embryogenesis. HSFI is best known for its role in regulating expression ofhsp70i, a stress-induced heat shock protein (hsp), although studies suggest that it may have roles in non-heat shock processes. Less is known regarding HSF2; however we recently found that HSF2 helps maintain the promoter of the hsp70i gene in a decompacted and accessible state during mitosis in a phenomenon called bookmarking (Science, accepted for publication, Nov. 2004). Our preliminary data suggests that the hsp70i gene is bookmarked in spermatozoa. The exact role ofhsp70i in fertilization and embryogenesis is not fully understood, although it is one of the first genes transcribed upon fertilization with transcription taking place predominantly in the male pronucleus. Bookmarking the hsp70i gene in spermatozoa makes particular sense given the large number of proteins that are synthesized and the various stresses that can occur early in embryogenesis. The ability to rapidly express the cytoprotective hsp70i protein would clearly promote embryonic vitality. There are a number of reproductive problems that can arise due to a deficiency, or excess of heat shock transcription factors. Due to the severity of these problems, including infertility, it is important to study HSFI and HSF2, and the genes they regulate and identify their various role(s) in reproduction. Not only will the work presented in this grant focus on identifying heat shock factor related problems at the molecular level that impair fecundity, but also initiate investigations into how heat shock transcription factors might be utilized as a contraceptive.