Figure 1.

Transcriptional regulation of TERT. (A) TERT transcription is mediated by the coordinated actions of myriad intracellular signaling pathways that are initiated by specific ligands (e.g., growth factors, cytokines). The downstream effectors of these receptor-ligand interactions activate (green arrow) or repress (red arrow) the expression of TERT as well as TFs that regulate TERT expression (1). As a consequence of transcriptional up- or downregulation, these TFs (represented by the green protein) are more or less able to engage the TERT promoter, both on their own (2) and in conjunction with accessory transcriptional regulators (represented by the pink and blue proteins) (3). These accessory factors include histone-modifying enzymes, which alter the chromatin landscape at the TERT promoter to facilitate or inhibit transcription (4). The diversity of signaling inputs and TFs that oversee TERT transcription enable combinatorial control of telomerase function in response to intracellular and extracellular conditions. (B) The human TERT promoter harbors binding sites for the major transcriptional regulators of TERT expression [shown as approximate nucleotide position relative to the transcription start site (TSS)] [64,65,66,67,68]. TFs shown above and below the chromosome (rectangle) have binding motifs located on overlapping segment of the TERT promoter, rather than binding in opposing orientations.