Tissue-specific expression of two human Ca_v1.2 isoforms under the control of distinct 5′ flanking regulatory elements

Abstract 

Transcriptional regulation may be important for L-type Ca²⁺ channel α_1C subunit (Ca_v1.2) gene expression. In this study, we found two human Ca_v1.2 isoforms, one strongly and selectively expressed in heart and the other with apparently ubiquitous expression. The promoter for the cardiac isoform has an ‘initiator’ sequence, and is active in neonatal cardiomyocytes but not in cardiac fibroblasts, H9C2 cells, human aorta-vascular smooth muscle and HEK293 cells. The promoter for the ubiquitously expressed isoform is of the ‘housekeeping’ type and is active in all cell types examined. These data indicate specific expression patterns of two human Ca_v1.2 isoforms under the control of distinct 5′ flanking regulatory sequences.

Keywords:  Exon, Heart failure, Regulatory element

Abbreviations:  Ca_v1.2, L-type Ca²⁺ channel α_1C subunit, CACNA1C, L-type Ca²⁺ channel α_1C subunit gene, TF, transcription factor, LV, left ventricle, HA-VSMC, human aorta vascular smooth muscle cells, 5′RACE, 5′ rapid amplification of cDNA ends, GSPs, gene-specific primers, FBS, fetal bovine serum, DMEM, Dulbecco’s modified Eagle’s medium, FW, forward primer, REV, reverse primer