Fig. 4.

hTERT transcription and promoter mutations. The hTERT gene is tightly repressed in almost all normal cells and tissues. Specific hTERT promoter mutations as part of cancer progression occur leading to increased transcription of hTERT. The transcription of hTERT is regulated by a series of transcription factors (TFs). hTERT promoter mutations create ETS/TCF binding motifs. Each mutation generates a new ETS/TCF binding site. Upregulating TFs such as ETS, c-MYC, SP1 and NF-kB bind to their respective sites and can promote hTERT transcription. Although binding of TFs is essential for hTERT transcription, in addition a permissive chromatin microenvironment is required. Binding of downregulating transcription factors decreases transcription. WT wild type; WT1 Wilms tumor protein1; MZF2 myeloid zinc finger protein 2