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The Role Of Thymine Dna Glycosylase (Tdg) And Dna Demethylation In Tgf Beta Signaling, Matthew E.R. Maitland
The Role Of Thymine Dna Glycosylase (Tdg) And Dna Demethylation In Tgf Beta Signaling, Matthew E.R. Maitland
Electronic Thesis and Dissertation Repository
Prompted by findings that TGFβ stimulates thymine DNA glycosylase (TDG) dependent rapid DNA demethylation and activation of the CDKN2B gene, I investigated the global role of TDG and DNA demethylation in TGFβ signaling in HaCaT cells. Using dot blot analysis, I show that TGFβ treatment increases the global levels of 5-formylcytosine, an intermediate metabolite of active DNA demethylation. Characterization of genomic regions that undergo DNA demethylation and recruitment of TDG indicate that they are both frequent events, but only overlap at 11 genomic locations. I identified 440 TGFβ upregulated genes, 40 of which were bound by TDG and 169 that …