GATA and FOG2 transcription factors differentially regulate the promoter for Kv4.2 K(+) channel gene in cardiac myocytes and PC12 cells.
Cardiovasc Res
; 60(2): 278-87, 2003 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-14613857
ABSTRACT
OBJECTIVE:
Kv4.2 subunits are major components of transient outward K(+) channels in cardiac myocytes and somatodendritic A-type channels in neurons. To identify molecular mechanisms underlying transcriptional regulation of Kv4.2 gene, we have isolated and characterized the promoter for the rat Kv4.2 gene.METHODS:
PCR-based amplification of cDNA end (5'RACE) and RNase protection assays were used to determine transcription start sites. Transient transfection of Kv4.2 promoter-luciferase reporter constructs into neonatal cardiac myocytes and PC12 cells was employed to measure activity of the Kv4.2 promoter. Cotransfection of expression vectors for the transcription factors, GATA and/or FOG2, was performed to determine the effects of these transcription factors on the Kv4.2 promoter.RESULTS:
Transcription of the gene initiates at 552 bp upstream from the translation initiation site in the brain and heart. Deletion analysis revealed that the approximately 200-bp fragment encompassing this start site drives significant transcription in neonatal cardiac myocytes and PC12 cells. The transcription factors GATA4 and 6 differentially enhance activity of the minimum promoter in the two cell types GATA4 produces a larger increase than GATA6 in cardiac myocytes, whereas the latter results in a more substantial enhancement in PC12 cells. Furthermore, the coregulator of GATA, FOG2, markedly suppresses the GATA-induced increase in myocytes, but enhances it in PC12 cells. The use of GATA mutants that are incapable of forming complexes with FOG2 indicates that the formation of GATA-FOG complexes is required for the FOG2-induced suppression in myocytes, but not for the FOG2-mediated enhancement in PC12 cells.CONCLUSION:
These results indicate that GATA and FOG2 transcription factors use distinct mechanisms to control the expression of Kv4.2 gene in cardiac myocytes and PC12 cells. The lack of a GATA-binding consensus sequence in the Kv4.2 minimum promoter suggests that these transcription factors indirectly influence the channel gene transcription.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Canais de Potássio
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Canais de Potássio de Abertura Dependente da Tensão da Membrana
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Região 5'-Flanqueadora
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Miócitos Cardíacos
/
Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article