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dc.contributor.advisorCevher, Murat Alper
dc.contributor.authorCanavar, Tuğçe
dc.date.accessioned2018-07-30T13:48:22Z
dc.date.available2018-07-30T13:48:22Z
dc.date.copyright2018-07
dc.date.issued2018-07
dc.date.submitted2018-07-20
dc.identifier.urihttp://hdl.handle.net/11693/47696
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2018.en_US
dc.descriptionIncludes bibliographical references (leaves 54-63).en_US
dc.description.abstractMediator is the most important coregulator in eukaryotic transcription. It conveys the signals received from transcriptional activators on enhancer sequences to transcription machinery on promoter regions. Although Mediator itself and MED1 subunit have been implicated in the activation of estrogen receptor alpha (ERα)-mediated gene expressions and breast cancer cell proliferations, the mechanism by which Mediator interacts and brings ligand-bound ERα on its cognate element site to promoter and translates their interactions to gene activation is still unknown. We aimed to identify the interaction between ERα and Mediator to clarify this mechanism. We recombinantly generated active human core Mediator complex along with other subunits of Mediator. We interestingly saw that MEDX showed a potential interaction. In addition to characterizing Mediator- ERα interaction, we also checked the role of the Mediator Complex in acquired tamoxifen resistance. We performed immobilized template recruitment assay to characterize the alterations in recruitment of Mediator subunits and RNA Pol II to 2XERE-TATA promoter in wild type and tamoxifen resistant MCF-7 cell lines. We tried to clarify how changes in pre-initiation complex formation causes resistance to tamoxifen in ERα-positive breast cancer patients. The increase in MEDZ subunit recruitment in resistant cells was striking and promising for further experiments. We hope that our findings will help to elucidate the detailed mechanism of ERα-dependent transcription and design alternative therapeutics.en_US
dc.description.statementofresponsibilityby Tuğçe Canavar.en_US
dc.format.extentxiv, 75 leaves : illustrations (some color) ; 30 cm.en_US
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectMediator Complexen_US
dc.subjectPre-initiation Complexen_US
dc.subjectTranscriptionen_US
dc.subjectTamoxifen Resistanceen_US
dc.titleInvestigating the role of the mediator complex in estrogen receptor alpha-mediated transcriptionen_US
dc.title.alternativeMediator kompleksin östrojen reseptörü alfanın düzenlediği transkripsiyondaki rolünün araştırılmasıen_US
dc.typeThesisen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.publisherBilkent Universityen_US
dc.description.degreeM.S.en_US
dc.identifier.itemidB158714
dc.embargo.release2019-01-20


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