The Role of DNA Methylation in Transcription Factor Activity

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Although it is well established that gene expression is closely correlated with DNA methylation, its role in regulating the activity of DNA-binding proteins remains unclear. It has recently been shown that Krüppel-like transcription factors (KLF) have distinct binding preferences for methylated DNA sequences. This project aims to investigate how the activity of transcription factors is dependent upon targeting of methylated DNA by defining the genome-wide set of sites and structural domains critical for binding. It also will explore the functional significance of these sequences using assays that investigate the importance of DNA methylation in KLF mediated cellular reprogramming to the pluripotent state.