TEF-1 and MEF2 transcription factors interact to regulate muscle-specific promoters.
Many muscle-specific genes are regulated by transcriptional enhancer factor-1 (TEF-1), serum response factor (SRF), and myocyte enhancer factor-2 (MEF2) transcription factors. TEF-1 interacts with the MADS domain of SRF and together SRF and TEF-1 co-activate the skeletal alpha-actin promoter. MEF2 factors also contain a MADS domain with 50% amino acid identity to the SRF MADS domain. Because of this sequence divergence, some SRF co-factors do not interact with MEF2. To demonstrate that TEF-1 factors could also interact with MEF2 through its MADS domain, we used co-immunoprecipitation and GST pull-down assays in vitro and a mammalian two-hybrid assay in vivo. The MADS domain was not sufficient for MEF2 interaction with TEF-1, because additional sequences in the activation domains of both proteins were required for in vivo association. The physiological significance of this interaction was also demonstrated by transient transfection assays using muscle-specific promoters. Our results suggest that by their interaction with MEF2 factors, TEF-1 factors can control MEF2-dependent muscle-specific gene expression.
Maeda
Tomoji
T
Cardiovascular Institute, School of Medicine, University of Pittsburgh, BST 1704.3, PA 15213, USA.
Gupta
Mahesh P
MP
Stewart
Alexandre F R
AF
D000199:Actins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D064326:MEF2 Transcription Factors; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D000199:Actins; D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D020033:Protein Isoforms; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; D008156:Luciferases; D005982:Glutathione Transferase