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

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

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DIMITROVA, Yoana, Nitish MITTAL, Souvik GHOSH, Beatrice DIMITRIADES, Daniel MATHOW, William Aaron GRANDY, Gerhard CHRISTOFORI, Mihaela ZAVOLAN, Andreas J. GRUBER, 2017. TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced epithelial to mesenchymal transition. In: Biology direct. BioMed Central. 12(1), 8. eISSN 1745-6150. Available under: doi: 10.1186/s13062-017-0180-7

@article{Dimitrova2017TFAP2-50911, title={TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced epithelial to mesenchymal transition}, year={2017}, doi={10.1186/s13062-017-0180-7}, number={1}, volume={12}, journal={Biology direct}, author={Dimitrova, Yoana and Mittal, Nitish and Ghosh, Souvik and Dimitriades, Beatrice and Mathow, Daniel and Grandy, William Aaron and Christofori, Gerhard and Zavolan, Mihaela and Gruber, Andreas J.}, note={Article Number: 8} }

Mathow, Daniel Mittal, Nitish Mathow, Daniel Background<br />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.<br /><br />Methods<br />From a computational analysis of a variety of high-throughput sequencing data sets we initially inferred that TFAP<sub>2</sub>A is connected to the core EMT network in both species. We then analysed publicly available human breast cancer data for TFAP<sub>2</sub>A 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.<br /><br />Results<br />We found that upon induction of EMT, the activity of TFAP<sub>2</sub>A, reflected in the expression level of its predicted targets, is up-regulated in a variety of systems, both murine and human, while TFAP<sub>2</sub>A’s expression is increased in more “stem-like” cancers. We provide strong evidence for the direct interaction between the TFAP<sub>2</sub>A TF and the ZEB<sub>2</sub> promoter and we demonstrate that this interaction affects ZEB<sub>2</sub> expression. Overexpression of TFAP<sub>2</sub>A from an exogenous construct perturbs EMT, however, in a manner similar to the downregulation of endogenous TFAP<sub>2</sub>A that takes place during EMT.<br /><br />Conclusions<br />Our study reveals that TFAP<sub>2</sub>A is a conserved component of the core network that regulates EMT, acting as a repressor of many genes, including ZEB<sub>2</sub>. Dimitriades, Beatrice 2020-09-21T09:01:49Z Ghosh, Souvik Dimitrova, Yoana Dimitriades, Beatrice Christofori, Gerhard 2017 2020-09-21T09:01:49Z Zavolan, Mihaela Zavolan, Mihaela Gruber, Andreas J. Mittal, Nitish Ghosh, Souvik Grandy, William Aaron TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced epithelial to mesenchymal transition Grandy, William Aaron eng terms-of-use Dimitrova, Yoana Christofori, Gerhard Gruber, Andreas J.

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