Transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene in response to TGF-b treatment

Abstract

Telomerase is important in cellular proliferative activity. Human telomerase reverse transcription (hTERT) is the catalytic subunit and key component of telomerase. The transcription of hTERT is limit-rate step of telomerase. Telomerase activity decreases in response to TGF-β. Through transient reporter assay, we find that hTERT promoter activity decreases, too. To identify the major regulatory element which contributes this decline of promoter activity, serial deletion analysis was done. As the result, we find that TGF-β represses hTERT promoter via E2F-site. The result of reporter assay with single mutant constructs on hTERT promoter agrees with this fact. Many promoter repressed in G0/G1 arrest are regulated by E2F-pocket protein complex via E2F-site. Through Chromatin IP assay, we confirmed that E2F4 and p130 bind to hTERT promoter in TGF-β treated HaCaT cells. Therefore, we suppose that E2F4-p130 complex through E2F-binding site regulate the hTERT promoter activity in response to TGF-β.