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dc.contributor.authorRambøl, Mia Marie-Elisabeth Hauge
dc.date.accessioned2014-03-10T22:09:53Z
dc.date.issued2013
dc.identifier.citationRambøl, Mia Marie-Elisabeth Hauge. An investigation on the possible role of Lsd1 in GR-mediated gene expression. Master thesis, University of Oslo, 2013
dc.identifier.urihttp://hdl.handle.net/10852/38769
dc.description.abstractSteroide hormone receptors (SHRs) are ligand-modulated transcription factors that regulate important physiological processes. The effects of SHRs are regulated by their coordinated interaction with other transcription factors, cofactors and components of the basal transcription machinery. Lysine specific demethylase 1 (LSD1) is an enzyme that influences chromatin structure by specifically demethylating H3K4me1/2. Human LSD1 has been found to act as a cofactor in SHR regulated transcription, and was shown to have a role in both ER-, AR- and PR-regulated gene expression. In addition, the association of LSD1 with AR and ER has been shown to change the substrate specificity of LSD1 from H3K4me1/2 to H3K9me1/2. In this study, we have investigated the possible role of mouse Lsd1 in GR-regulated gene expression. We report here the direct physical interaction of Lsd1 with GR, and ligand dependent recruitment of Lsd1 to Glucocorticoid response elements (GREs). We show that pharmacological inhibition of Lsd1 impairs GR-dependent gene expression, implicating Lsd1 as a potential coactivator for GR. Several GR-activated genes displayed increased demethylation of H3K4me2 and H3K9me2 at their GREs upon ligand binding, coinciding with Lsd1 recruitment. Further, we show that the local chromatin environment at specific GREs is affected by Lsd1 inhibition in an unexpected fashion, reducing the level of both H3K4me2 and H3K9me2. Surprisingly, however, siRNA mediated knockdown of Lsd1expression did not recapitulate these effects induced by pharmacological inhibition of Lsd1. These data have implications for possible Lsd1 role on GR-regulated gene expression.eng
dc.language.isoeng
dc.subjectepigenetics
dc.subjectgene
dc.subjectregulation
dc.subjectchromatin
dc.subjectmodifications
dc.subjectsteroid
dc.subjecthormone
dc.subjectreceptors
dc.titleAn investigation on the possible role of Lsd1 in GR-mediated gene expressioneng
dc.typeMaster thesis
dc.date.updated2014-03-10T22:09:53Z
dc.creator.authorRambøl, Mia Marie-Elisabeth Hauge
dc.date.embargoenddate3013-11-29
dc.rights.termsDette dokumentet er ikke elektronisk tilgjengelig etter ønske fra forfatter. Tilgangskode/Access code A
dc.identifier.urnURN:NBN:no-42169
dc.type.documentMasteroppgave
dc.rights.accessrightsclosedaccess
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/38769/1/Rambl---Master.pdf


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