The goals of my proposed research are to elucidate the functions of the Aurora-B kinase in chromosome segregation and epigenetic reprogramming during spermatogenesls. This research promises to provide new information pertaining to infertility and diseases arising from chromosomal abnormalities such as cancer and Down syndrome. In mitotic cells the Aurora-B kinase has key functions in chromosome dynamics, chromosome condensation and chromatin modifications. However, its function in mammalian meiosis is unkno wn. I propose to investigate the role of the Aurora-B kinase in mammalian spermatogenesis using newly engineered transgenic mouse lines with meiotic-specific promoters that either over-express Aurora-B, or express a non-functional form that acts as a domin ant negative. Immunofluorescence and electron microscopy will be used to analyse the alignment, synapsis and segregation of the chromosomes in transgenic versus wild type mice. In addition to its role in chromosome dynamics, the Aurora-B kinase is likely t o have an epigenetic function in germ cells. The field of epigenetics involves the study of heritable modifications that do not alter the DNA code, but instead control gene transcription through chromatin structure via histone modifications. Epigenetic mod ifications in the germline are remarkable because they can control gene expression from one generation of an organism to the next. Aurora-B is known to phosphorylate, histone H3. This phosphorylation has been linked to chromatin condensation and epigenetic regulation of gene expression. To investigate the role of Aurora-B in the epigenetic program of sperm cells I will probe for differences in chromatin modifications between transgenic and wild type animals.
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