Fatma Dogan ( Poster and Three Minute Thesis )
School of Medicine
Poster
Telomerase activity regulation is promoter methylation-sensitive
Telomeres protect human chromosome ends from degradation . Telomerase is responsible for telomere maintenance and elongation where the telomerase reverse transcriptase gene ( hTERT ) encodes the rate-limiting catalytic subunit . Promoter methylation has been suggested to be associated with epigenetic control of telomerase regulation which holds significant potential for therapy . Here we sought to understand promoter methylation patterns in pluripotent stem , somatic , and cancer cells .
Cells were cultured in either an air oxygen standard incubator or a 2 % O2 controlledoxygen workstation . hTERT gene expression and telomerase activity significantly decreased in both conditions during differentiation of pluripotent stem cells . Telomerase activity was significantly higher in physiologic oxygen vs . air cultured cells . Consistent with the above telomerase activity levels correlated with slower onset of differentiation in physiological oxygen conditions . Significantly , hypermethylation of TERT promoter region during differentiation process was associated with suppressed hTERT gene expression and telomerase enzyme activity . Methylation analysis from pluripotent , cancer and somatic cells demonstrated a distinct methylation signature that distinguished somatic and pluripotent stem cells from cancer cells .
In conclusion , promoter hypermethylation could be responsible for downregulated telomerase activity in differentiation process . A distinct methylation pattern provides a potential novel therapeutic strategy to inhibit TERT expression without affecting healthy tissue .
Postgraduate Conference 2020 Page 18