Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo

Maria Kotini, Elias H. Barriga, Jonathan Leslie, Marc Gentzel, Verena Rauschenberger, Alexandra Schambony and Roberto Mayor ()
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Maria Kotini: University College London
Elias H. Barriga: University College London
Jonathan Leslie: University College London
Marc Gentzel: Max Planck Institut for Molecular Cell Biology and Genetics
Verena Rauschenberger: Friedrich-Alexander University Erlangen-Nuremberg
Alexandra Schambony: Friedrich-Alexander University Erlangen-Nuremberg
Roberto Mayor: University College London

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract Connexins are the primary components of gap junctions, providing direct links between cells under many physiological processes. Here, we demonstrate that in addition to this canonical role, Connexins act as transcriptional regulators. We show that Connexin 43 (Cx43) controls neural crest cell migration in vivo by directly regulating N-cadherin transcription. This activity requires interaction between Cx43 carboxy tail and the basic transcription factor-3, which drives the translocation of Cx43 tail to the nucleus. Once in the nucleus they form a complex with PolII which directly binds to the N-cadherin promoter. We found that this mechanism is conserved between amphibian and mammalian cells. Given the strong evolutionary conservation of connexins across vertebrates, this may reflect a common mechanism of gene regulation by a protein whose function was previously ascribed only to gap junctional communication.

Date: 2018
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DOI: 10.1038/s41467-018-06368-x

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