Enhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transition

Alotaibi H, Basilicata MF, Shehwana H, Kosowan T, Schreck I, Braeutigam C, Konu O, Brabletz T, Stemmler M (2015)

Publication Type: Journal article

Publication year: 2015

Journal

BBA - Biochimica et Biophysica Acta Elsevier

Book Volume: 1849

Pages Range: 731-42

Journal Issue: 6

DOI: 10.1016/j.bbagrm.2015.01.005

Abstract

Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) highlight crucial steps during embryogenesis and tumorigenesis. Induction of dramatic changes in gene expression and cell features is reflected by modulation of Cdh1 (E-cadherin) expression. We show that Cdh1 activity during MET is governed by two enhancers at +7.8kb and at +11.5kb within intron 2 that are activated by binding of Grhl3 and Hnf4?, respectively. Recruitment of Grhl3 and Hnf4? to the enhancers is crucial for activating Cdh1 and accomplishing MET in non-tumorigenic mouse mammary gland cells (NMuMG). Moreover, the two enhancers cooperate via Grhl3 and Hnf4? binding, induction of DNA-looping and clustering at the promoter to orchestrate E-cadherin re-expression. Our results provide novel insights into the cellular mechanisms whereby cells respond to MET signals and re-establish an epithelial phenotype by enhancer cooperativity. A general importance of our findings including MET-mediated colonization of metastasizing tumor cells is suggested.

Authors with CRIS profile

Thomas Brabletz Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Marc Stemmler Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung

Involved external institutions

Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics DE Germany (DE) Bilkent University / Bilkent Üniversitesi TR Turkey (TR)

How to cite

APA:

Alotaibi, H., Basilicata, M.F., Shehwana, H., Kosowan, T., Schreck, I., Braeutigam, C.,... Stemmler, M. (2015). Enhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transition. BBA - Biochimica et Biophysica Acta, 1849(6), 731-42. https://dx.doi.org/10.1016/j.bbagrm.2015.01.005

MLA:

Alotaibi, Hani, et al. "Enhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transition." BBA - Biochimica et Biophysica Acta 1849.6 (2015): 731-42.

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