Defense Date

2016

Document Type

Thesis

Degree Name

Master of Science

Department

Human Genetics

First Advisor

Dr. Shirley Taylor

Abstract

The role of cytosine modifications on nuclear transcription has been well characterized, but the function of DNA methylation in the mitochondrial genome has not been determined. Previous studies conducted by the Taylor laboratory have shown overexpression of the mitochondrial isoform of DNMT1 leads to strand-specific changes in gene expression. Here, we show that increased mtDNMT1 expression leads to an increase in the polycistronic transcript encoding the ND1 and Cox1 sequences. In order to understand the mechanistic basis of these changes, we investigated the effects of CpG methylation in the heavy strand promoter on transcription initiation and TFAM binding. Methylation was found to increase transcription initiation from HSP1 and result in larger TFAM:DNA complexes forming at lower protein concentrations. Our data suggest a functional role for cytosine methylation in the mitochondria, which we propose may have an effect on oxidative phosphorylation and cellular function.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

4-22-2016

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