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A Promoter in the Coding Region of the Calcium Channel Gene CACNA1C Generates the Transcription Factor CCAT.

Authors :
Gomez-Ospina, Natalia
Panagiotakos, Georgia
Portmann, Thomas
Pasca, Sergiu P.
Rabah, Dania
Budzillo, Agata
Kinet, Jean Pierre
Dolmetsch, Ricardo E.
Source :
PLoS ONE; Apr2013, Vol. 8 Issue 4, p1-11, 11p
Publication Year :
2013

Abstract

The C-terminus of the voltage-gated calcium channel Ca<subscript>v</subscript>1.2 encodes a transcription factor, the calcium channel associated transcriptional regulator (CCAT), that regulates neurite extension and inhibits Ca<subscript>v</subscript>1.2 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 Ca<subscript>V</subscript>1.2. Expression of CCAT is independent of Ca<subscript>v</subscript>1.2 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 Ca<subscript>V</subscript>1.2. 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
8
Issue :
4
Database :
Complementary Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
87677507
Full Text :
https://doi.org/10.1371/journal.pone.0060526