VITO-1 is an essential cofactor of TEF1-dependent muscle-specific gene regulation.
The expression of several muscle-specific genes is partially or completely regulated by MCAT elements, which bind members of the TEF family of transcription factors. TEF1 itself is unable to activate reporter plasmids bearing TEF1-binding sites, suggesting that additional bridging or co-activating factors are necessary to allow interaction of TEF1 with the transcriptional machinery. In addition, none of the known TEF genes are exclusively expressed in the cardiac or skeletal muscle lineage to account for the muscle-specific expression of MCAT-dependent genes. Here we describe that VITO-1, a new SID (scalloped interaction domain)-containing protein, binds to TEF1 in vitro and strongly stimulates transcription of a MCAT reporter plasmid together with TEF-1. Since VITO-1 is predominantly expressed in the skeletal muscle lineage, it might serve as an essential transcriptional intermediary factor to promote muscle-specific expression via MCAT cis-regulatory elements. Although VITO-1 alone is not sufficient to initiate myogenic conversion of 10T1/2 fibroblastic cells, it enhanced MyoD-mediated myogenic conversion. In addition, interference with VITO-1 expression by siRNA attenuated differentiation of C2C12 muscle cells and MyoD-dependent myogenesis in 10T1/2 cells. We conclude that VITO-1 is a crucial new cofactor of the muscle regulatory programme.
Günther
Stefan
S
Institute of Physiological Chemistry, University of Halle-Wittenberg, Hollystrasse 1, 06097 Halle, Germany.
Mielcarek
Michal
M
Krüger
Marcus
M
Braun
Thomas
T
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D024510:Muscle Development; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D009687:Nuclear Proteins; D009928:Organ Specificity; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D017570:MyoD Protein; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; C483778:Vgll2 protein, mouse