The MEF-3 motif is required for MEF-2-mediated skeletal muscle-specific induction of the rat aldolase A gene.
The rat aldolase A gene contains two alternative promoters and two alternative first exons. The distal promoter M is expressed at a high level only in skeletal muscle. Previous in vitro transfection studies identified the region from -202 to -85 as an enhancer that is responsible for dramatic activation during the differentiation of chicken primary myoblasts. This enhancer contains an A/T-rich sequence resembling the MEF-2 motif, which is an important element of muscle enhancers and promoters. In this study, we demonstrate that the MEF-2 sequence is essential but not sufficient for the activity of the enhancer. Another region required for the activity was recognized by a nuclear factor, tentatively named MAF1. MAF1 was found in both muscle cells and nonmuscle cells, and MAF1 from both cell types was indistinguishable by gel retardation and DNase I footprint experiments. The sequence required for MAF1 binding is very similar to the MEF-3 motif, which is an element of the skeletal muscle-specific enhancer of the cardiac troponin C gene. Because MAF1 and MEF-3 are closely related in both recognition sequence and distribution, MAF1 and MEF-3 probably represent the same nuclear factor which may play an important role in muscle gene transcription. Thus, the muscle-specific induction of the aldolase A gene is governed by muscle-specific MEF-2 and existing MEF-3 (MAF1).
Hidaka
K
K
Department of Bioscience, National Cardiovascular Center Research Institute, Osaka, Japan.
Yamamoto
I
I
Arai
Y
Y
Mukai
T
T
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002642:Chick Embryo; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004790:Enzyme Induction; D005634:Fructose-Bisphosphate Aldolase / Q000096:biosynthesis / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D064326:MEF2 Transcription Factors; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology / Q000201:enzymology*; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; D005634:Fructose-Bisphosphate Aldolase