Regulation of telomerase expression by Hox gene family transcriptional factors
Ng, Joscelyn Jun Quan
Date of Issue2016-05-12
School of Biological Sciences
Duke-NUS Medical School
In recent years, cancer has been the leading cause of death in Singapore. One of the hallmarks of cancer cells is its limitless potential to replicate. Most cancer cells maintain its telomere length through re-activation of telomerase activity which are absent in normal differentiated cells. Telomerase activity is unique in cancer and stem cells, equipping these two types of cells with limitless replicative potential. Human telomerase enzyme composed mainly of two components: telomerase reverse transcriptase (TERT) and telomerase RNA (TERC) with TERT being the limiting factor in determining telomerase activity in vitro. Therefore, regulation of hTERT expression plays a crucial role in activating telomerase. Hox proteins are important transcription factors that induces stem cell differentiation during human embryogenesis. Through past laboratory work, HoxC5 was found to regulate telomerase activity directly however the underlying mechanism remains unclear. This study focuses on understanding the interaction between HoxC5 and its cofactor Meis 1, Meis 2 and Meis 3 in terms of hTERT regulation. Lentiviral vector containing Meis 3 was cloned and co-immunoprecipitation results showed that HoxC5 interacts specifically with Meis 3. In addition, overexpression of both HoxC5 and Meis 3 in HeLa cells led to a decrease in hTERT expression level.
Final Year Project (FYP)
Nanyang Technological University