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Nat Commun. 2018 Sep 21;9(1):3846. doi: 10.1038/s41467-018-06368-x.

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

Author information

1
Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK.
2
London Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.
3
Max Planck Institut for Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307, Dresden, Germany.
4
Center for Molecular and Cellular Bioengineering, Facility Molecular Analysis/Mass Spectrometry, TU Dresden, Tatzberg 47/49, 01307, Dresden, Germany.
5
Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, 91058, Germany.
6
Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK. r.mayor@ucl.ac.uk.

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.

PMID:
30242148
PMCID:
PMC6155008
DOI:
10.1038/s41467-018-06368-x
[Indexed for MEDLINE]
Free PMC Article

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