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

Kotini, M; Barriga, EH; Leslie, J; Gentzel, M; Rauschenberger, V; Schambon, A; Mayor, R; (2018) Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo. Nature Communications , 9 , Article 3846. 10.1038/s41467-018-06368-x. Green open access

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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.

Type: Article
Title: Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-018-06368-x
Publisher version: https://doi.org/10.1038/s41467-018-06368-x
Language: English
Additional information: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Keywords: Cell adhesion, Cell migration, Morphogenesis
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10057233
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