Polyglutamine represses cAMP-responsive-element-mediated transcription without aggregate formation
2005
Transcriptional dysregulation, particularly cAMP-responsive-ele ment-mediated transcriptional repression, has been implicated it expanded polyglutamine diseases. However, it has not been clari fied whether this transcriptional repression is a cause or result o neurodegeneration. Furthermore, the association between aggre gates of expanded polyglutamine stretches and transcriptional re pression is not clear. We established isogenic cell lines with polyglutamine stretches, which also expressed d2EGFP under th< control of cAMP-responsive elements. In this system, the polyglu tamine stretch repressed cAMP-responsive-element-mediated n transcription without the formation of macroscopic expanded i- polyglutamine aggregates. Furthermore, aggregate formation if did not have an adverse effect on the repression of transcriptional activity. The results demonstrated that the repression of cAMPresponsive-element-mediated transcription is an early event h caused by a soluble form of polyglutamine stretch.
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