Date of Award


Degree Type


Degree Name

Master of Science




Dr. Nathalie Bérubé

Second Advisor

Dr. Mellissa Mann

Third Advisor

Dr. David Haniford


X-linked a-thalassaemia mental retardation (ATR-X) syndrome is characterized by severe cognitive delay, broad developmental abnormalities and a-thalassaemia. Disease-causing mutations in the ATRX gene give rise to a malfunctioning protein and result in aberrant DNA methylation at specific repeat sequences. ATRX is a SNF2 chromatin remodeling protein that targets α-globin gene expression, but additional targets remain largely elusive. Using a mouse model in which Atrx is conditionally deleted in the developing forebrain, I show that DNA methylation at repeat sequences is comparable to that found in ATR-X patients. I further describe the identification of specific imprinted genes that are progressively regulated by Atrx throughout development. I show that aberrant imprinted gene expression in the Atrxnull brain is not correlated with changes in DNA methylation at regulatory differentially methylated regions, but that Atrx colocalizes with MeCP2 at the H19 ICR. Taken together, my findings establish for the first time a link between ATRX and the control of neuronal imprinted gene expression.



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