Abstract 1033: Transcriptional factor ZBP-89 interacts with DNMT1 and HDAC3 to regulate Bak expression

Abstract

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide with a very high mortality. Because the success of the conventional therapies is limited, epigenetic therapy may represent an alternative for HCC management. The present study was designed to investigate whether DNA methyltransferases and histone acetylases were involved in regulation of ZBP-89-induced Bak expression. After adenovirus Ad-ZBP-89 transfection, bisulfate modificated DNA sequencing, immunofluorence staining, siRNA interference, western blotting, and enzymatic activity assays were used to analyze DNA methylation, histone modifications and the enzyme activity in human HCC cell. Based on our previous report that ZBP-89 up-regulated Bak expression, the current study revealed that ZBP-89 regulated Bak expression through interacting with HDAC3 and DNMT1. ZBP-89 could also demethylate the CpG island in Bak promoter to facilitate Bak expression and apoptosis. Additionally, ZBP-89 contributed to maintain histone H3 and H4 acetylation by inhibiting HDACs activity. ZBP-89 was found to suppress DNMT1 activity and HDAC3 activity. Conclusively, our study demonstrates a novel mechanism how the transcription factor ZBP-89 mediates epigenetic modification to promote Bak expression. The new pathway discovered may help to develop certain epigenetic therapy against HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1033. doi:1538-7445.AM2012-1033