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논문검색

Fission Yeast-Based Screening to Identify Putative HDAC Inhibitors using a Telomeric Reporter Strain

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.

저자정보

  • Jiwon Ahn Genome Research Center, KRIBB
  • Chung-Hae Choi Genome Research Center, KRIBB
  • Won-Yong Jung Genome Research Center, KRIBB
  • Mi-Ryoung Kim Genome Research Center, KRIBB
  • Chang-Mo Kang Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS
  • Chun-Ho Kim Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS
  • Hee-Moon Park College of Microbiology
  • Kyung-Bin Song Agriculture and Life Science, Chungnam National University
  • Misun Won Genome Research Center, KRIBB
  • Kyung-Sook Chung Genome Research Center, KRIBB

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