TPE suppresses genes at chromosomal ends of neuroblastoma cells with long telomeres. The average of the percentage of repressive chromatin ChromHMM states at chromosomal ends, subtelomeric region referred to as “T” and genome-wide referred to as “G” for all coding and noncoding sequences (A) and genic regions (B) in neuroblastoma cells with short and long telomeres. C and D, Pharmacologic inhibition of EZH2 induces TERT expression in TERT-negative neuroblastoma cells. C, Western blot analysis for H3K27me3 and H3K27 total in neuroblastoma cells after treatment with tazemetostat or the drug vehicle only. D, Fold change of TERT expression in the same cells after the same treatment measured by qRT-PCR. E and F, Inhibiting EZH2 facilitates MYCN binding to the TERT promoter in neuroblastoma cells with long telomeres. ChIP-qPCR enrichment of MYCN at the TERT promoter in SKNMMMYCN (E) and SKNJCIMYCN (F) after treating the cells with tazemetostat for 3 weeks and doxycycline induction of MYCN for 2 days. As MYCN is not expressed in both cell lines, MYCN enrichment in the absence of doxycycline represents background. *, P < 0.05, error bars represent SD.
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Graham et al. (2024) studied this question.
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