Investigation of the genomic conditions for DMR acquisition in mammalian oocytes

Genomic imprinting, a complex and essential epigenetic phenomenon in mammals, regulates gene expression in a parent-of-origin specific manner. The majority of imprinted genes are regulated by differentially methylated regions (DMRs), wherein DNA methylation is differently marked between the paternal and maternal alleles. Intriguingly, while the number of maternally imprinted DMRs varies among different mammalian groups, the molecular mechanisms underlying the acquisition of such novel lineage-specific imprinted DMRs remain elusive. This project aims to advance our understanding of the interplay between pre-existing genetic context (i.e. protein binding motifs) and new genetic changes (i.e. novel transcription) in the process of acquiring imprinted DMRs in the mammalian genome. To address this, the prime objective of this project is to establish novel DNA methylation domains, by inducing expression of otherwise repressed genes in oocytes, and characterise the epigenetic status of novel methylated regions after fertilisation. My research has the potential, not only to advance our understanding of the evolutionary mechanisms of genomic imprinting, but also to provide clues to address why such a phenomenon exists, and has evolved, only in marsupial and eutherian mammals. By transferring the expertise of the host lab, which has pioneered the model of transcription-dependent establishment of DNA methylation in mammalian oocytes, this project will also support me in establishing myself as a leading independent researcher in the field of epigenetics.