Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Fission Yeast-based Screening to Identify Putative HDAC Inhibitors Using a Telomeric Reporter Strain

  • Chung, Kyung-Sook (Medical Genome Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ahn, Jiwon (Medical Genome Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Choi, Chung-Hae (Medical Genome Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Yim, Nam Hui (Medical Genome Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kang, Chang-Mo (Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Chun-Ho (Laboratory of Cytogenetics and Tissue Regeneration, Korea Institute of Radiological and Medical Sciences) ;
  • Lee, Kyeong (Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Hee-Moon (College of Microbiology, Chungnam National University) ;
  • Song, Kyung-Bin (Department of Food Science and Technology, Chungnam National University) ;
  • Won, Misun (Medical Genome Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2008.01.08
  • Accepted : 2008.02.27
  • Published : 2008.07.31
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Abstract

Transcriptional silencing is regulated by promoter methylation and histone modifications such as methylation and acetylation. We constructed a Schizosaccaromyces pombe reporter strain, KCT120a, to identify modifiers of transcriptional silencing, by inserting the $ura4^+$ gene into a heterochromatic telomere region. Two compounds inhibited the activity of histone deacetylases, induced acetylation of histone H3 and caused apoptotic cell death in HeLa cells. Expression of gelsolin and $p21^{waf1/cip1}$ also increased, as it does in response to HDAC inhibitors such as TSA. Therefore, these compounds appear to be potent inhibitors of HDACs, and hence potential anti-cancer drugs. Our observations suggest that a yeast cell-based assay system for transcriptional silencing may be useful for identifying histone deacetylase inhibitors and other agents affecting chromatin remodeling.

Keywords

Acknowledgement

Supported by : Korea Research Council of Fundamental Science and Technology

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