Abstract 2326: Understand the telomerase-dependent transcriptional regulation in cancer cells

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA We and others have previously demonstrated that modulation of telomerase activity induces rapid and defined changes in genome-wide gene expression profiles in telomerase-positive cancer cells in culture, which point to the possibility of telomerase's involvement in gene regulation. Previous results also indicated the direct involvement of telomerase catalytic subunit-hTERT in transcriptional regulation through its interaction with Brg1 as well as NFkB. Such transcriptional function of hTERT is not dependent on its reverse transcriptase activity, suggesting a novel telomere-independent function of telomerase that promote stem cell proliferation and survival via activation of key genes regulating cell proliferation and survival. To further explore the potential role of hTERT in direct regulation of genome-wide gene expression in cancer cells, we have engineered cancer cells expressing 3xFlag-tagged hTERT from endogenous loci using AAV-mediated recombination. These genetically engineered cells allow the reliable detection and immunopurification of endogenous and functional hTERT in cancer cells. Such unique tools provide the key to identify potential transcriptional targets regulated by hTERT directly in vivo. Using ChIP-seq, we have mapped the genome-wide targets of potential hTERT binding sites in both HeLa S3 cells and HCT116 cells. Citation Format: TingDong Yan, Chang-Ching Liu, Lai-Fong Poon, Xiaoran Chai, Melissa Jane Fullwood, Sujoy Ghosh, Shang Li. Understand the telomerase-dependent transcriptional regulation in cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2326. doi:10.1158/1538-7445.AM2014-2326