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Regulation of α1G T-type calcium channel gene (CACNA1G) expression during neuronal differentiation

Authors

  • Gabriel E. Bertolesi,

    1. Laboratory for Retina and Optic Nerve Research, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    2. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    3. Department of Physiology & Biophysics, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
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  • Christine A. B. Jollimore,

    1. Laboratory for Retina and Optic Nerve Research, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    2. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
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  • Chanjuan Shi,

    1. Laboratory for Retina and Optic Nerve Research, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    2. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
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  • Lindsy Elbaum,

    1. Laboratory for Retina and Optic Nerve Research, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    2. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    3. Department of Physiology & Biophysics, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
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  • Eileen M. Denovan-Wright,

    1. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
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  • Steven Barnes,

    1. Laboratory for Retina and Optic Nerve Research, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    2. Department of Physiology & Biophysics, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    3. Department of Ophthalmology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
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  • Melanie E. M. Kelly

    1. Laboratory for Retina and Optic Nerve Research, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    2. Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
    3. Department of Ophthalmology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7, Canada
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: Dr M. Kelly, Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, B3H 4H7 Canada.
Tel: 902-494-3325; Fax: 902-494-6309; E-mail: mkelly@dal.ca

Abstract

Down-regulation of T-type Ca channel current and mRNA occurs following differentiation of Y79 retinoblastoma cells. To understand how the decrease in expression is linked to cell differentiation, we examined transcriptional regulation of the Cav3.1 Ca channel gene, CACNA1G. We identified two putative promoters (A and B) in 1.3 kb of cloned genomic DNA. Reverse transcriptase-polymerase chain reaction and 5′ rapid amplification of cDNA ends-polymerase chain reaction analyses demonstrated that two transcripts with different 5′ untranslated regions are generated by different transcription start sites, with promoter A favoured in undifferentiated cells and promoter B favoured in differentiated cells. Functional analyses of the promoter sequence revealed that both promoters are active. Enhancer and repressor sequences were identified upstream of promoter A and B, respectively. These results suggest that the down-regulation of α1G mRNA in differentiated Y79 cells is mediated primarily by decreased activity of promoter A, which could occur in conjunction with repression of the activity of promoter B. The decrease in T-type Ca channel expression in Y79 cells may be an essential signal affecting phenotypic maturation and expression of other ion channel subtypes in the differentiated cells.

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