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Type: Journal article
Title: Specificity protein 1 (Sp1) maintains basal epithelial expression of the miR-200 family: implications for epithelial-mesenchymal transition
Author: Kolesnikoff, N.
Attema, J.
Roslan, S.
Bert, A.
Schwarz, Q.
Gregory, P.
Goodall, G.
Citation: Journal of Biological Chemistry, 2014; 289(16):11194-11205
Publisher: The American Society for Biochemistry and Molecular Biology
Issue Date: 2014
ISSN: 0021-9258
Statement of
Natasha Kolesnikoff, Joanne L. Attema, Suraya Roslan, Andrew G. Bert, Quenten P. Schwarz, Philip A. Gregory and Gregory J. Goodall
Abstract: Epithelial-mesenchymal transition (EMT) is required for the specification of tissues during embryonic development and is recapitulated during the metastatic progression of tumors. The miR-200 family plays a critical role in enforcing the epithelial state with their expression lost in cells undergoing EMT. EMT can be mediated by activation of the ZEB1 and ZEB2 (ZEB) transcription factors, which repress miR-200 expression via a self-reinforcing double negative feedback loop to promote the mesenchymal state. However, it remains unclear what factors drive and maintain epithelial-specific expression of miR-200 in the absence of EMT-inducing factors. Here, we show that the transcription factor Specificity Protein 1 (Sp1) binds to the miR-200b∼200a∼429 proximal promoter and activates miR-200 expression in epithelial cells. In mesenchymal cells, Sp1 expression is maintained, but its ability to activate the miR-200 promoter is perturbed by ZEB-mediated repression. Reduction of Sp1 expression caused changes in EMT-associated markers in epithelial cells. Furthermore, we observed co-expression of Sp1 and miR-200 during mouse embryonic development wherein miR-200 expression was only lost in regions with high ZEB expression. Together, these findings indicate that miR-200 family members require Sp1 to drive basal expression and to maintain an epithelial state.
Keywords: Epithelial mesenchymal transition; Metastasis; MicroRNA; Sp1; Transcription; ZEB transcription factor; miR-200
Rights: © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
RMID: 0030014951
DOI: 10.1074/jbc.M113.529172
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Appears in Collections:Medicine publications

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