Fig. 5. TERT interacts with β-Catenin-containing transactivation complex and is recruited to the promoters of specific target genes in AD neurons.

a, List of TERT-interacting proteins identified by mass spectrometry in human iPSC-derived APP^Dp neurons. b, RNA-Seq heat map of WNT signaling pathway genes in EGFP- and TERT-transduced human iPSC-derived APP^Dp neurons (n = 3). c, Co-immunoprecipitation of endogenous β-Catenin (active), CREBBP, POLR2A, and TERT from human iPSC-derived APP^Dp neurons. d, In vitro binding assay between human TERT and β-Catenin. e, Schematic of full-length and truncated forms of human TERT. The upper panel represents four domains of TERT protein as the TERT N-terminal (TEN) domain, the TERT-specific RNA-binding domain (TRBD), the reverse transcriptase (RT) domain and the C-terminal extension (CTE)/thumb domain. f, Co-immunoprecipitation of endogenous β-Catenin with the full-length and truncated forms of 3xFlag-TERT. g, ChIP-Seq density heat maps of TERT, β-Catenin (active) and TCF7 across the gene promoters of human iPSC-derived APP^Dp neurons. h, Chromatin-state maps showing β-Catenin (active), TCF7 and TERT binding peaks for the WNT9B, ATP1A3, HSPA12A, HSPA6, and MYC locus, as determined by ChIP-Seq. Experiments in c, d and f were repeated three times independently with similar results.