Research Project
6413509
DESCRIPTION: (Adapted from the applicant's abstract) In mammals, a small number of genes are regulated such that their expression is dependent on parent-of-origin. These imprinted genes retain their parental identity via an imprinting mark that serves to distinguish the parental alleles from each other and regulate their expression accordingly. One candidate for the mark that distinguishes the parental alleles is the methylation of cytosine residues in CpG dinucleotides, an epigenetic modification that can be reset in the germline of each individual such that the appropriate imprint is transmitted to offspring. The objective of this research is to enhance the understanding of the erasure and establishment of imprinting marks during mouse germline development. The significance of establishing the appropriate imprint is illustrated by the fact that in the absence of parent-of-origin-specific expression, developmental defects ensue, causing human diseases such as Prader-Willi, Angelman and Beckwith-Weidemann Syndromes. The first goal of this research is to determine when paternal-specific methylation is erased at the imprinted mouse H19 gene. Second, this research will test the hypothesis that the establishment of parent-specific methylation patterns during germ cell development is coordinately regulated by comparing the temporal pattern of methylation establishment for the paternally-methylated mouse p57 gene with that of the H19 gene. This research will advance the field of imprinting by determining whether the establishment of imprinting marks is globally or independently controlled. In addition, it will provide information regarding the time of imprinting mark erasure during gametogenesis, which has not been described for any imprinted gene. Finally, it will enhance undergraduate education by providing students the opportunity to conduct independent research on a molecular genetic project.
