[{"key":"dc.contributor.author","value":"Reid, Kimberly Jane","language":null},{"key":"dc.date.accessioned","value":"2009-08-06T23:46:56Z","language":null},{"key":"dc.date.available","value":"2009-08-06T23:46:56Z","language":null},{"key":"dc.date.issued","value":"2001","language":null},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/11966","language":null},{"key":"dc.description.abstract","value":"Genes uniquely regulated by the androgen receptor (AR) typically contain\r\nmultiple androgen response elements (AREs) that in isolation are of low DNA\r\nbinding affinity and transcriptional activity. However, specific combinations of\r\nAREs in their native promoter context results in highly cooperative DNA binding by\r\nAR and high levels of transcriptional activation. Within this study, we demonstrate\r\nthat the natural androgen-regulated promoters of PSA and Probasin contain two\r\nclasses of AREs dictated by their primary nucleotide sequence that function to\r\nmediate cooperativity. Class I AR-binding sites display conventional guanine\r\ncontacts. Class II AR-binding sites have distinctive atypical sequence features and\r\nupon binding to AR the DNA structure is dramatically altered through allosteric\r\ninteractions with the receptor. Class II sites stabilize AR-binding to adjacent Class I\r\nsites and result in synergistic transcriptional activity and increased hormone\r\nsensitivity. The specific nucleotide variation within the androgen receptor binding\r\nsites dictate was determined to dictate differential functions to the receptor. The\r\npotential role of individual nucleotides within Class II sites and predicted consensus\r\nsequences for Class I and II sites was also identified. Our data suggest that this may\r\nbe a universal mechanism by which AR achieved unique regulation of target genes\r\nthrough complex allosteric interactions dictated by primary binding sequences.","language":"en"},{"key":"dc.format.extent","value":"6580006 bytes","language":null},{"key":"dc.format.mimetype","value":"application\/pdf","language":null},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":null},{"key":"dc.rights","value":"For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https:\/\/open.library.ubc.ca\/terms_of_use.","language":null},{"key":"dc.title","value":"Cooperative binding mechanisms leading to the specific androgen receptor regulation of target genes","language":"en"},{"key":"dc.type","value":"Text","language":null},{"key":"dc.degree.name","value":"Master of Science - MSc","language":"en"},{"key":"dc.degree.discipline","value":"Pathology","language":""},{"key":"dc.degree.grantor","value":"University of British Columbia","language":null},{"key":"dc.date.graduation","value":"2001-11","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Medicine, Faculty of","language":"en"},{"key":"dc.description.affiliation","value":"Pathology and Laboratory Medicine, Department of","language":"en"},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]