Date of Award

2017

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Ryba, Tyrone

Area of Concentration

Biology

Abstract

Previous studies have shown that DNA methylation directs the localization of H3K27me3, a histone modification in chromatin deposited by the PRC2 protein complex at silenced genes and intergenic regions. Demethylation by knockout of the so called de novo DNA methyltransferase genes, Dnmt3a and Dnmt3b, and the gene for the maintenance DNA methyltransferase, Dnmt1, results in the non-canonical localization of H3K27me3 marks. As these two antagonistic marks are often associated with different types of chromatin (PcG-silenced chromatin as in facultative heterochromatin for H3K27me3 and constitutive heterochromatin for DNA methylation), it was predicted that regions newly devoid of DNA methylation would result in enrichment of H3K27me3 in these regions and changes in replication timing, which reflects the time at which segments of chromatin are replicated during S-phase. Here, we investigated the effects of DNA methylation on replication timing in wildtype and mutant mouse embryonic stem cells (mESCs). Although further research is needed, it appears that the loss of DNA methylation in the mESCs did not result in a significant change in the global replication timing of the genome, but did have significant localized effects on replication timing. In addition, our data found no discernable relationship between changes in replication timing and localization of H3K27me3 marks.

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