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DREAM-mediated Regulation of GCM1 in the Human Placental Trophoblast

The trophoblast transcription factor glial cell missing-1 (GCM1) regulates asymmetric division of placental cytotrophoblast to form the differentiated syncytiotrophoblast. Reduced GCM1 expression is a key feature of the hypertensive disorder preeclampsia. In-silico techniques identified a novel calcium-dependent transcriptional repressor – DREAM as a regulatory candidate for GCM1. The overall objective of this thesis was to determine if DREAM regulates GCM1 expression and therefore villous trophoblast turnover. siRNA-mediated DREAM silencing in both BeWo cells and floating villous explants significantly upregulated GCM1 causing reduced cytotrophoblast proliferation. Calcium-dependency was demonstrated in both BeWo cells and floating villous explants by contrasting the effects of ionomycin and nimodipine. A direct interaction between DREAM and the GCM1 promoter was demonstrated using EMSA and ChIP assay. DREAM is a negative upstream regulator of GCM1 expression in human placenta that participates in calcium-dependent trophoblast differentiation.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/24234
Date05 April 2010
CreatorsBaczyk, Dorota
ContributorsLye, Stephen J.
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
Languageen_ca
Detected LanguageEnglish
TypeThesis

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