XXXX proximal and core promoter elements dictate @entity16815 dependence and transcriptional repression by histone deacetylase inhibitors.

@entity1 @entity7242 @entity5 @entity16815 @entity4910 @entity994
Histone deacetylase inhibitors (HDIs) induce cell cycle arrest, differentiation, or apoptosis in numerous @entity5 cell types both in vivo and in vitro. These dramatic effects are the result of a specific reprogramming of gene expression. However, the mechanism by which these agents activate the transcription of some genes, such as @entity994 ( @entity994 ), but repress others, such as @entity4910 , is currently unknown. We have been studying the @entity1 @entity7242 gene as a model for HDI-mediated transcriptional repression. We found previously that both the tissue-specific and housekeeping @entity7242 promoters were equally repressed by HDIs. Here we show that, despite an overt dissimilarity, both @entity7242 promoters do share similar core promoter elements and transcription is @entity16815 dependent. Detailed analysis of the @entity7242 promoters suggested that both core and proximal promoter elements were responsible for HDI-mediated repression. This was confirmed in a series of promoter-swapping experiments with the HDI-inducible, @entity16815 -independent @entity994 ( @entity994 ) promoter. Remarkably, all the @entity7242 - @entity994 ( @entity994 ) chimeric promoter constructs were not only repressed by HDIs but also dependent on @entity16815 . Together these experiments suggest that the overall promoter architecture, rather than discrete response elements, is responsible for HDI-mediated repression, and they implicate core promoter elements in particular as potential mediators of this response.
