Basal and alpha1-adrenergic-induced activity of minimal rat betaMHC promoters in cardiac myocytes requires multiple TEF-1 but not NFAT binding sites
| Autor: | Iain K. Farrance, Katherine S. Lee, B. Gail McLean, Paul C. Simpson |
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| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Molecular Sequence Data Biology Muscle hypertrophy Ventricular Myosins Transcription (biology) Internal medicine medicine Myocyte Animals Myocytes Cardiac Binding site Promoter Regions Genetic Molecular Biology Transcription factor Binding Sites Base Sequence NFATC Transcription Factors Skeletal muscle Nuclear Proteins TEA Domain Transcription Factors NFAT Promoter Cell biology Rats DNA-Binding Proteins medicine.anatomical_structure Endocrinology Mutation Adrenergic alpha-1 Receptor Agonists Cardiology and Cardiovascular Medicine Transcription Factors |
| Zdroj: | Journal of molecular and cellular cardiology. 35(5) |
| ISSN: | 0022-2828 |
| Popis: | A culture model for cardiac hypertrophy, stimulation of neonatal rat cardiac myocytes by alpha(1)-adrenergic agonists, has been used extensively to identify transcription factors that activate genes during cardiac hypertrophy, such as skeletal alpha-actin, beta-myosin heavy chain (betaMHC), and B-natriuretic peptide. We used this culture model to further investigate transcription factors regulating the betaMHC promoter in cardiac myocytes under basal conditions and during hypertrophy. We found that the rat betaMHC promoter contains two other MCAT sites, in addition to the two MCATs reported previously. The four MCAT sites are conserved in some but not all of the mammalian betaMHC promoters examined, and all bind TEF-1 but with varying affinity. As assayed by transient transfection into cardiac myocytes, the four MCATs within 348 bp of the transcription start site are required for full activity of the rat betaMHC promoter in the absence and presence of the alpha(1)-adrenergic agonist phenylephrine (PE). We found that the betaMHC promoter also contains a binding site for the NFAT family of transcription factors, which are activated by calcineurin and are implicated in the hypertrophic process. Although this site bound NFAT3 in vitro and has been reported to be required for betaMHC promoter activity in slow skeletal muscle, mutation of the site had no effect on basal or on PE-induced activity of the promoter in cardiac myocytes. Our results show that full activity of minimal betaMHC promoters in the presence and absence of hypertrophic agents requires multiple MCAT sites but not NFAT-binding sites. |
| Databáze: | OpenAIRE |
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