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The role of TET1 and TET1ALT in cancer
Good, Charly Ryan
Good, Charly Ryan
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Thesis/Dissertation
Date
2017
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Biomedical Sciences
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http://dx.doi.org/10.34944/dspace/2919
Abstract
DNA hypermethylation is known to contribute to the formation of cancer and this process has been widely studied. However, DNA hypomethylation has received far less attention and the factors controlling the balance between hypo and hypermethylation and its impact on tumorigenesis remains unclear. TET1 is a DNA demethylase that regulates DNA methylation, hydroxymethylation and gene expression. Full length TET1 (TET1FL) has a CXXC domain that binds to un-methylated CG islands (CGIs). This CXXC domain allows TET1 to protect CGIs from aberrant methylation but it also limits its ability to regulate genes outside of CGIs. This dissertation reports a novel isoform of TET1 (TET1ALT) that has a unique transcription start site from an alternate promoter in intron 2, yielding a protein with a unique translation start site. Importantly, TET1ALT lacks the CXXC domain but retains the catalytic domain. TET1ALT is repressed in ESCs but becomes activated in embryonic and adult tissues while TET1FL is ex
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