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TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced epithelial to mesenchymal transition

Dimitrova, Yoana and Gruber, Andreas J. and Mittal, Nitish and Ghosh, Souvik and Dimitriades, Beatrice and Mathow, Daniel and Grandy, William Aaron and Christofori, Gerhard and Zavolan, Mihaela. (2017) TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced epithelial to mesenchymal transition. Biology Direct, 12 (1). p. 8.

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Official URL: http://edoc.unibas.ch/55024/

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Abstract

The transition between epithelial and mesenchymal phenotypes (EMT) occurs in a variety of contexts. It is critical for mammalian development and it is also involved in tumor initiation and progression. Master transcription factor (TF) regulators of this process are conserved between mouse and human.; From a computational analysis of a variety of high-throughput sequencing data sets we initially inferred that TFAP2A is connected to the core EMT network in both species. We then analysed publicly available human breast cancer data for TFAP2A expression and also studied the expression (by mRNA sequencing), activity (by monitoring the expression of its predicted targets), and binding (by electrophoretic mobility shift assay and chromatin immunoprecipitation) of this factor in a mouse mammary gland EMT model system (NMuMG) cell line.; We found that upon induction of EMT, the activity of TFAP2A, reflected in the expression level of its predicted targets, is up-regulated in a variety of systems, both murine and human, while TFAP2A's expression is increased in more "stem-like" cancers. We provide strong evidence for the direct interaction between the TFAP2A TF and the ZEB2 promoter and we demonstrate that this interaction affects ZEB2 expression. Overexpression of TFAP2A from an exogenous construct perturbs EMT, however, in a manner similar to the downregulation of endogenous TFAP2A that takes place during EMT.; Our study reveals that TFAP2A is a conserved component of the core network that regulates EMT, acting as a repressor of many genes, including ZEB2.; This article has been reviewed by Dr. Martijn Huynen and Dr. Nicola Aceto.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Dimitrova, Yoana Aleksandrova and Gruber, Andreas J. and Mittal, Nitish and Ghosh, Souvik and Dimitriades, Beatrice and Grandy, William Aaron and Christofori, Gerhard M. and Zavolan, Mihaela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:BioMed Central
e-ISSN:1745-6150
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:05 Oct 2017 07:30
Deposited On:05 Oct 2017 07:30

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