Investigating the relationship between transcription factors and DNA methylation in breast cancer.

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A common feature of tumour cells, across all tissues in the body, is a dramatic change in the genomic landscape of DNA methylation - a epigenetic modification which has been shown to regulate chromatin structure and gene expression. DNA methylation is observed globally in normal cell genomes, whilst regions with significantly more dense methylation, called CpG islands, are most commonly found in promoter regions and associate with repressed gene expression. It is predicted that this reduced gene expression is a consequence of the interactions between DNA methylation and transcription factors, whereby DNA methylation marks may either directly impede transcription factor biding or the recruitment of transcription factors to edit the local epigenetic landscape. However, there is currently little evidence to support a mechanistic model for this interaction. In tumour cells, there is marked hypomethylation observed across the genome, whilst a number of hypermethylated promoter regions are also evident. This phenotype may suggest that the interaction between DNA methylation and transcription factors has a role in processes such as oncogene activation and the dysregulation of tumour suppressor genes, which are responsible for controlling cell proliferation and progression through the cell cycle. Therefore, our aim is to interrogate the relationship between DNA methylation and transcription factors in cancer cells in comparison with normal cell genomic data. This can be achieved using genetic approaches, whereby established methQTLs can be used to determine genomic regions in cancer genomes which associate with significant changes in DNA methylation.