The Role of Thymine DNA Glycosylase (Tdg) and DNA Demethylation in TGF Beta Signaling

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...

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Bibliographic Details
Main Author:	Maitland, Matthew E. R
Format:	Dissertation
Language:	English
Published:	ProQuest Dissertations & Theses 01-01-2015
Subjects:	Apoptosis Biochemistry Bioinformatics Cancer Cell cycle Cell division Cellular biology Chemistry Developmental biology DNA methylation DNA polymerase DNA repair Enzymes Epigenetics Gene expression Genetics Genomes Leukemia Metabolites Oncology Oxidation Phosphorylation Polypeptides Scientific imaging Signal transduction Stem cells Steroids
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Summary:	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 exhibited DNA demethylation. Distribution of the location of TDG peaks and DNA demethylation regions to the gene promoter suggests that these events occur at distal elements. These results suggest that TDG and DNA demethylation could be important factors involved in TGFβ’s regulation of gene expression.
ISBN:	9798841712626