The Glucocorticoid receptor (GR) is one of many steroid hormone receptors. It controls broad physiological gene networks, confers pathological effects in a range of disease states, and offers an excellent target for therapeutic intervention. Therefore, it is necessary to better understand the mechanisms of GR regulation. In particular, we are interested in better understanding the protein-nucleotide interactions (transcription factors interacting with transcription factor binding sites). Upon glucocorticoids-hormone binding, the GR forms a protein-nucleotide interaction with a specific transcription factor binding site known as a glucocorticoid response element (GRE). This research has employed three different but complementary bioinformatics approaches to identify Mouse genes putatively transcriptionally regulated by GR. Firstly, we focus on the problem of searching for putative GREs in the complete Mouse genome using a position weight matrix. This produced a large number of putative GREs. Most of these are likely false positive predictions. Secondly, two different strategies are used to improve the accuracy of our framework: combinatorial analysis of multiple TFs/modules of TFBSs and phylogenetic footprinting (PF). The number of putative GREs can be reduced by 97.9% using the module of TFBSs analysis, 97.7% using the PF analysis, and 99.9% using both module and PF analyses. In each step, a statistical test has been used to measure the significance of the results.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.82437 |
| Date | January 2005 |
| Creators | Tang, Zuojian, 1967- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (School of Computer Science.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002227301, proquestno: AAIMR12552, Theses scanned by UMI/ProQuest. |
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