A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells
- PMID: 16652385
- DOI: 10.1002/pros.20451
A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells
Abstract
Background: The connexin 43 gene (cx43, GJA1) mediates gap junctional intercellular communication (GJIC), which regulates tissue homeostasis. cx43 is frequently downregulated in prostate cancer. We investigated the role of a histone deacetylase (HDAC)-dependent mechanism in the transcriptional repression of cx43 in a panel of prostate cancer cells.
Methods: The impact of Trichostatin A (TSA), an inhibitor of HDAC, on exogenous and endogenous cx43 gene transcription was examined by the luciferase assay, Northern blot, nuclear run-on, Western blot, and chromatin immunoprecipitation assays.
Results: Trichostatin A induces transcription of cx43 gene and GJIC. The co-activator p300/CBP synergizes with TSA for cx43 promoter activation. We identified a promoter region where cooperation between Ap1 and Sp1 elements was essential for TSA-induced cx43 transcription. TSA increased the level of hyperacetylated histones bound to cx43 promoter.
Conclusion: Our results highlight the potential utility of inhibitors of HDAC to restore cx43 gene expression in prostate cancer.
(c) 2006 Wiley-Liss, Inc.
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