Orphan nuclear receptors recruit TRIM28 to promote telomeric H3K9me3 for the ALT pathway

ABSTRACT: Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism deployed in embryonic stem cells and cancer cells. High levels of the heterochromatin mark H3 lysine 9 trimethylation (H3K9me3) at telomeres are critical for ALT, but how this is achieved remains unclear. Telomeric association of orphan nuclear receptors (NRs)-such as COUP-TF1, COUP-TF2, TR2, and TR4-has been shown previously to facilitate ALT activation. Here, we show that orphan NRs regulate telomeric H3K9me3 through TRIM28, a corepressor of ZNF transcription factors, to promote ALT. We report that H3K9me3 is induced by telomeric association of orphan NRs in cultured human fibroblast and ALT cancer cell lines. Moreover, TRIM28 is required for the orphan-NR-induced H3K9 methylation and ALT phenotypes. Important

SUBMITTER: Chia Tsen Tsai 

PROVIDER: S-SCDT-10_1038-S44318-026-00760-W | biostudies-other |

REPOSITORIES: biostudies-other