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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Cell Movement
  • Connexin 43 / metabolism*
  • DNA Polymerase II / metabolism
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Neural Crest / physiology*
  • Nuclear Proteins / metabolism
  • Transcription Factors / metabolism
  • Xenopus laevis


  • Cadherins
  • Connexin 43
  • Nuclear Proteins
  • Transcription Factors
  • transcription factor BTF3
  • DNA Polymerase II