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Differentiation. 2009 Jun;77(5):492-504. doi: 10.1016/j.diff.2008.12.005. Epub 2009 Feb 23.

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.

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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.


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.

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