Transcriptional enhancer factor-1 in cardiac myocytes interacts with an alpha 1-adrenergic- and beta-protein kinase C-inducible element in the rat beta-myosin heavy chain promoter.
In cultured rat cardiac myocytes, a 20-base pair sequence (-215/-196) of the rat beta-myosin heavy chain (MHC) promoter mediates induction by both alpha 1-adrenergic stimulation and a constitutively activated beta-protein kinase C (PKC), and binds cardiac myocyte nuclear factor(s) through an "enhancer core" element (5'-TGTGG-TATG-3') (Kariya, K., Karns, L. R., and Simpson, P. C. (1994) J. Biol. Chem. 269, in press). Here, we report identification of this enhancer core binding factor as the rat homologue of transcriptional enhancer factor-1 (TEF-1), a human transcription factor for viral enhancers. In gel mobility shift and immunoblot analyses, the myocyte factor and human TEF-1 were indistinguishable in terms of sequence recognition, mobility, and immunoreactivity. Furthermore, DNA binding activity for the beta-MHC enhancer core and TEF-1 immunoreactivity correlated closely. These results are the first to suggest a role for TEF-1 in transcriptional regulation by PKC. The data also provide direct evidence for interaction of TEF-1 with the beta-MHC promoter, supporting a function for TEF-1 in regulation of cellular gene expression, as well as viral, and outline a pathway for alpha 1-adrenergic regulation of beta-MHC gene transcription in cardiac myocytes.
Kariya
K
K
Division of Cardiology and Research Service, Veterans Affairs Medical Center, San Francisco, California 94121.
Farrance
I K
IK
Simpson
P C
PC
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009218:Myosins / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D018340:Receptors, Adrenergic, alpha-1; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; D011493:Protein Kinase C; D009218:Myosins