원문정보
초록
영어
Transcriptional silencing is regulated by promoter methylation and histone modifications, such as methylation and acetylation. As a a model system to search for modifiers of transcriptional silencing, we constructed a Schizosaccaromyces pombe reporter strain, KCT120a, to study transcriptional silencing by inserting the ura4+ gene into a telomere, one of the heterochromatin regions. The strain KCT120a was used to investigate compounds that are involved in the modification of transcriptional silencing.
Among them, two compounds, reproducibly positive by dose-dependent assays in a screen system, inhibited the activity of histone deacetylases and subsequently induced the acetylation of histone H3 and apoptotic cell death in HeLa cells. The expressions of gelsolin and p21waf1/cip1 were also increased by the two compounds in a manner consistent with HDAC inhibitors such as TSA. Therefore, they might also be potent inhibitors of HDACs, making them possible anti-cancer drugs. This result suggests that a yeast cell-based assay system for transcriptional silencing is very useful for identifying histone deacetylase inhibitors and other agents involved in the modification of chromatin remodeling.