SNF2H-Mediated Chromatin Remodelling and Its Regulation of the Pluripotent State

FieldValue
dc.contributor.authorCook, David
dc.date.accessioned2016-09-01T17:59:04Z
dc.date.available2016-09-01T17:59:04Z
dc.date.issued2016
dc.identifier.urihttp://hdl.handle.net/10393/35097
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-5368
dc.description.abstractIn embryonic stem cells (ESCs), the SWI/SNF, CHD, and INO80 families of ATP-dependent chromatin remodellers have been implicated in maintaining pluripotency-associated gene expression, however the involvement of ISWI family remodellers has yet to be defined. Here, we explore the importance of the mammalian ISWI homologue SNF2H (Smarca5) by deriving a conditional knockout mouse ESC line and observing the consequences of SNF2H depletion on the pluripotent state. Cre-mediated deletion of Snf2h disrupts hallmark characteristics of pluripotency, resulting in distinct morphological changes; reduced expression of the master transcription factors Oct4, Sox2, and Nanog; and reduced alkaline phosphatase activity. To understand the mechanisms of SNF2H-mediated regulation, we mapped SNF2H-bound nucleosomes genome-wide. SNF2H is broadly distributed across the genome, but is preferentially enriched at active regulatory regions and transcription factor binding sites. These findings demonstrate the importance of SNF2H in ESCs and shed light on genome-wide mechanisms of transcriptional regulation.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectChromatin
dc.subjectRemodelling
dc.subjectPluripotency
dc.subjectEpigenetics
dc.subjectSequencing
dc.subjectBioinformatics
dc.titleSNF2H-Mediated Chromatin Remodelling and Its Regulation of the Pluripotent State
dc.typeThesis
dc.contributor.supervisorVanderhyden, Barbara
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
CollectionThèses, 2011 - // Theses, 2011 -

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