Grant: Discovery Grants Program - Individual

IDENTIFICATION AND EVOLUTIONARY COMPARISON OF IMPRINTING CENTERS Genomic imprinting is a specialized transcriptional regulatory mechanism that restricts expression to the maternally- or paternally-inherited copy of a gene. An intriguing characteristic of imprinted genes is that they often cluster in larger chromosomal domains that are regulated by imprinting centers. The growing number of imprinted domains provides a strong argument for conservation of key epigenetic features that regulate these domains. However, despite many advances, the nature of the imprinting center and its mode of action have remained elusive. The short-term objectives of this research proposal are (1) determine the role of the Kcnq1ot1 noncoding RNA in imprinted domain establishment during preimplantation development, (2) identify novel ICs and imprinted domains, and (3) to perform comparative genomic analyses amongst various vertebrates to identify common regulatory elements. Preimplantation is a unique period in mammalian development. It is the ONLY time when the entire genome undergoes global reprogramming with the exception of small number of regions. Taking advantageous of this unique developmental feature, we performed a bioinformatic analyses of methylation in oocytes, sperm and embryos and identified 11 candidate imprinting centers. We will determine their imprinted status. Neighbouring genes will then be examined to determine whether they are regulated by the associated imprinting center. Comparative analysis of current genomic databases will be performed on imprinting centers and surrounding regions among different mammals and other vertebrates to identify common regulatory elements. Data generated from this study will allow comparative analysis of a larger number of imprinting centers and will lead to a greater understanding of the molecular mechanisms regulating imprinting and the evolution of genomic imprinting.