Fig. 1: TERT promoter activation requires the additional ETS binding site provided by a wildtype sequence duplication or a mutation. | Nature Communications

Fig. 1: TERT promoter activation requires the additional ETS binding site provided by a wildtype sequence duplication or a mutation.

From: Conserved features of TERT promoter duplications reveal an activation mechanism that mimics hotspot mutations in cancer

Fig. 1

a TERTp wildtype schematic. Overlapping native ETS motifs are shown relative to the TERT ATG translational start site. b TERTp hotspot mutation schematic. Native ETS motif and de novo ETS motifs (hotspot mutations) are shown with GABP tetramer binding to the G228A mutation and native ETS motif along with the relative position of the TERT ATG. Distance (bp) and number of helical turns (HT) between the native ETS motif and de novo motifs (hotspot mutations) are shown. c TERTp duplication schematic. Native ETS motif and de novo ETS motif (duplication) are shown relative to the TERT ATG. Distance (bp) between the native ETS motif and de novo ETS motif (duplication) is shown along with the associated helical turns (HT). The figures were created with BioRender (a–c). d TERTp luciferase reporter assays for wild type, hotspot mutants and duplications at 24 h after transfection in UMUC3 bladder cancer cells. Values are mean and SD. N = 2 independent experiments. e TERTp luciferase reporter assays for wildtype, hotspot mutants and duplications at 24 h in LN229 glioblastoma cells. Values are mean and SD. N = 2 independent experiments. f All possible 22 bp TERTp duplications spanning the native ETS motif and beyond are shown along with their DNA sequence including the duplication insertion point in bold, location of de novo and native ETS motifs are in red and green font, respectively, and associated reporter activity from Fig. 1d, e. The following duplication sequences generate identical variant sequence upon insertion into the TERTp: −88_−67 = −89_−68, −90_−69; −91_−70 = −92_−71; −94_−73 = −95_−74, −96_−75, −97_−76, −98_−77; −101_−80 = −102_−81, −103_−82; −105_−84 = −106_−85, −107_−86, −108_−87, −109_−88; and −112_−91 = −113_−92. Thus, all 20 unique duplications were interrogated with reporter assays while all 34 duplication sequences are shown in panel f for reference and comparison. Abbreviations: TERTp, TERT promoter. Source data are provided as a Source Data file.

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