The transcriptional repressor ZBP-89 and the lack of Sp1/Sp3, c-Jun and Stat3 are important for the down-regulation of the vimentin gene during C2C12 myogenesis.
Currently, considerable information is available about how muscle-specific genes are activated during myogenesis, yet little is known about how non-muscle genes are down-regulated. The intermediate filament protein vimentin is known to be "turned off" during myogenesis to be replaced by desmin, the muscle-specific intermediate filament protein. Here, we demonstrate that vimentin down-regulation is the result of the combined effect of several transcription factors. Levels of the positive activators, Sp1/Sp3, which are essential for vimentin expression, decrease during myogenesis. In addition, c-Jun and Stat3, two additional positive-acting transcription factors for vimentin gene expression, are also down-regulated. Over-expression via adenoviral approaches demonstrates that the up-regulation of the repressor ZBP-89 is critical to vimentin down-regulation. Elimination of ZBP-89 via siRNA blocks the down-regulation of vimentin and Sp1/Sp3 expression. From these studies we conclude that the combinatorial effect of the down-regulation of positive-acting transcription factors such as Sp1/Sp3, c-Jun and Stat3 versus the up-regulation of the repressor ZBP-89 contributes to the "turning off" of the vimentin gene during myogenesis.
Salmon
Morgan
M
Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University, School of Medicine, PO Box 980614 Richmond, VA 23298-0614, USA.
Zehner
Zendra E
ZE
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D016758:Genes, jun; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D032448:Myoblasts, Skeletal / Q000166:cytology; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics; D051705:Sp3 Transcription Factor / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics*
D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D014746:Vimentin; C491741:Zfp148 protein, mouse; D051705:Sp3 Transcription Factor