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- W4387537193 abstract "Abstract Activation of human telomerase (hTERT) and resulting maintenance of telomeres is widely understood. Whether telomeres, on the other hand, influence hTERT regulation is relatively less studied. We found hTERT was transcriptionally up/down regulated depending on telomere length (TL), but independent of telomere looping. Cells from different tissues, engineered for either telomere elongation/shortening gave increase/decrease in hTERT , respectively. Temporal increase of TL, followed by decrease over days, resulted in induction and subsequent repression of hTERT , supporting the causal role of TL. Further confirmed by TL-dependent promoter activity from exogenously inserted hTERT reporter. Mechanistically, we show non-telomeric TRF2 binding at the hTERT promoter to be TL-dependent. Promoter bound TRF2 recruited the canonical PRC2-complex inducing repressor histone H3K27-trimethylation. Together, these reveal a heretofore unaddressed model of telomere homeostasis in telomerase-positive cells, where TL-dependent hTERT levels in turn maintain long/short telomeres. This might help better understand telomere-related physiologies like cancer, ageing and pluripotency." @default.
- W4387537193 created "2023-10-12" @default.
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- W4387537193 date "2023-10-10" @default.
- W4387537193 modified "2023-10-18" @default.
- W4387537193 title "Telomeres control regulation of the human Telomerase (hTERT) gene through non-telomeric TRF2 and independent of Telomere looping" @default.
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- W4387537193 doi "https://doi.org/10.1101/2023.10.09.561466" @default.
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