Muscle-enriched TEF-1 isoforms bind M-CAT elements from muscle-specific promoters and differentially activate transcription.
M-CAT elements mediate cardiac- and embryonic skeletal muscle-specific expression of the cardiac troponin T gene and a number of other cardiac-specific genes. M-CAT binding factor was shown to be related to cloned human TEF-1, a transcriptional regulator of the SV40 viral enhancer. Here we describe the cloning of TEF-1 from chick heart and the identification of several novel isoforms. We show that TEF-1 mRNA is considerably enriched in cardiac and skeletal muscle, consistent with a proposed role in muscle gene transcription. The predominant TEF-1 isoforms, TEF-1A and a novel isoform TEF-1B, bind M-CAT elements with high affinity and in a sequence-specific manner. We further demonstrate that the C-terminal portion of TEF-1B, which contains the 13-amino acid exon that distinguishes this isoform, can activate transcription when linked to a heterologous DNA binding domain, while the same domain of TEF-1A cannot. Therefore, isoforms of TEF-1 may play different roles in the regulation of M-CAT-dependent promoters in striated muscle cells.
Stewart
A F
AF
Department of Anatomy, University of California, San Francisco 94143.
Larkin
S B
SB
Farrance
I K
IK
Mar
J H
JH
Hall
D E
DE
Ordahl
C P
CP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002642:Chick Embryo; D002645:Chickens; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005091:Exons; D015870:Gene Expression; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D009132:Muscles / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors