A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.

The C-terminus of the voltage-gated calcium channel Cav1.2 encodes a transcription factor, the calcium channel associated transcriptional regulator (CCAT), that regulates neurite extension and inhibits Cav1.2 expression. The mechanisms by which CCAT is generated in neurons and myocytes are poorly un...

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Main Authors: Natalia Gomez-Ospina, Georgia Panagiotakos, Thomas Portmann, Sergiu P Pasca, Dania Rabah, Agata Budzillo, Jean Pierre Kinet, Ricardo E Dolmetsch
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3628902?pdf=render
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author Natalia Gomez-Ospina
Georgia Panagiotakos
Thomas Portmann
Sergiu P Pasca
Dania Rabah
Agata Budzillo
Jean Pierre Kinet
Ricardo E Dolmetsch
author_facet Natalia Gomez-Ospina
Georgia Panagiotakos
Thomas Portmann
Sergiu P Pasca
Dania Rabah
Agata Budzillo
Jean Pierre Kinet
Ricardo E Dolmetsch
author_sort Natalia Gomez-Ospina
collection DOAJ
description The C-terminus of the voltage-gated calcium channel Cav1.2 encodes a transcription factor, the calcium channel associated transcriptional regulator (CCAT), that regulates neurite extension and inhibits Cav1.2 expression. The mechanisms by which CCAT is generated in neurons and myocytes are poorly understood. Here we show that CCAT is produced by activation of a cryptic promoter in exon 46 of CACNA1C, the gene that encodes CaV1.2. Expression of CCAT is independent of Cav1.2 expression in neuroblastoma cells, in mice, and in human neurons derived from induced pluripotent stem cells (iPSCs), providing strong evidence that CCAT is not generated by cleavage of CaV1.2. Analysis of the transcriptional start sites in CACNA1C and immune-blotting for channel proteins indicate that multiple proteins are generated from the 3' end of the CACNA1C gene. This study provides new insights into the regulation of CACNA1C, and provides an example of how exonic promoters contribute to the complexity of mammalian genomes.
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spelling doaj.art-3c045b6804ce476589d73826acd0cd672022-12-22T00:29:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6052610.1371/journal.pone.0060526A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.Natalia Gomez-OspinaGeorgia PanagiotakosThomas PortmannSergiu P PascaDania RabahAgata BudzilloJean Pierre KinetRicardo E DolmetschThe C-terminus of the voltage-gated calcium channel Cav1.2 encodes a transcription factor, the calcium channel associated transcriptional regulator (CCAT), that regulates neurite extension and inhibits Cav1.2 expression. The mechanisms by which CCAT is generated in neurons and myocytes are poorly understood. Here we show that CCAT is produced by activation of a cryptic promoter in exon 46 of CACNA1C, the gene that encodes CaV1.2. Expression of CCAT is independent of Cav1.2 expression in neuroblastoma cells, in mice, and in human neurons derived from induced pluripotent stem cells (iPSCs), providing strong evidence that CCAT is not generated by cleavage of CaV1.2. Analysis of the transcriptional start sites in CACNA1C and immune-blotting for channel proteins indicate that multiple proteins are generated from the 3' end of the CACNA1C gene. This study provides new insights into the regulation of CACNA1C, and provides an example of how exonic promoters contribute to the complexity of mammalian genomes.http://europepmc.org/articles/PMC3628902?pdf=render
spellingShingle Natalia Gomez-Ospina
Georgia Panagiotakos
Thomas Portmann
Sergiu P Pasca
Dania Rabah
Agata Budzillo
Jean Pierre Kinet
Ricardo E Dolmetsch
A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.
PLoS ONE
title A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.
title_full A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.
title_fullStr A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.
title_full_unstemmed A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.
title_short A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.
title_sort promoter in the coding region of the calcium channel gene cacna1c generates the transcription factor ccat
url http://europepmc.org/articles/PMC3628902?pdf=render
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