Pdx1 is a transcription factor of fundamental importance to pancreas formation and adult islet ?-cell function. However, little is known regarding its role in mature b-cells or the positive- and negative-acting coregulators recruited to mediate transcriptional control. Using a conditional deletion and lineage tracing strategy we revealed a bifunctional role of Pdx1 in maintenance of mature ?-cell identity as Pdx1-deleted cells rapidly lost b-cell features and simultaneously acquired a global transcriptional profile similar to ?-cells. To better understand how Pdx1 mediates its actions in mature b-cells, a coimmunoprecipitation/mass spectrometry approach was undertaken. Numerous Pdx1-interacting factors possessing a wide range of cellular functions linked with this protein, including, but not limited to, coregulators associated with transcriptional activation and repression, DNA damage response, and DNA replication were isolated. Because chromatin remodeling activities are essential to developmental lineage decisions and adult cell function, our analysis focused on investigating the influence of the Swi/Snf chromatin remodeler on Pdx1 action.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-05272015-163131 |
| Date | 28 May 2015 |
| Creators | McKenna, Brian Douglas |
| Contributors | Maureen Gannon, Richard O'Brien, Tony Weil, Chris Wright |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-05272015-163131/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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