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 / Biomedical Sciences
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/2937 |
| Date | January 2017 |
| Creators | Good, Charly Ryan |
| Contributors | Issa, Jean-Pierre, Engel, Nora, Sapienza, Carmen, Bellacosa, Alfonso |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 151 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/2919, Theses and Dissertations |
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