Allele specific re-establishment of imprinted DNA methylation using epigenome editing

Through unknown mechanisms, parent-of-origin-specific methylation marks on one allele of imprinted genes are able to escape the embryonic reprogramming wave occurring during the first week of development and retain their profiles via DNA methylation maintenance activity. Failing to maintain proper genomic imprinting patterns during the embryonic reprogramming leads to various abnormal developmental delay. What remains to be elucidated is whether we can permanently re-establish normal profiles of DNA methylation and subsequent gene expression of imprinted (allele-specific) sequences following the loss of their DNA methylation imprinting status. To set the foundation for a clear understanding of the mechanisms behind re-establishing the loss of inherited methylation profiles, we hypothesize that we can re-establish specifically and permanently the lost DNA methylation imprints at specific loci by targeted epigenome editing in embryonic cells. Under the guidance of a senior PhD student, the MITACS intern will use a CRISPR epigenome editing system to add or remove site specific DNA methylation marks on imprinted regions in a model of embryonic stem cells, and define if we can properly re-establish DNA methylation imprints and associated gene expression following their dysregulation. This project will further the understanding of the fundamental complex biochemical mechanisms of TOBECONT’.

Faculty Supervisor:

Serge McGraw

Student:

Partner:

Universidad Nacional Autónoma de México

Discipline:

Life Sciences

Sector:

Education

University:

Université de Montréal

Program: