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Cancer cells utilize the alternative lengthening of telomeres (ALT) mechanism to maintain telomere length, bypass cellular senescence, and achieve replicative immortality. Researchers led by Associate Research Fellow Dr. Liuh-Yow Chen at the Institute of Molecular Biology, Academia Sinica, discovered that orphan nuclear receptors recruit the transcriptional corepressor TRIM28 to telomeres, where it promotes H3K9me3 deposition and facilitates ALT activation. Mechanistically, orphan nuclear receptors recruit TRIM28 to telomeric chromatin through protein–protein interactions, thereby facilitating heterochromatin remodeling and functionally linking chromatin reorganization to ALT activation. These findings highlight the essential role of TRIM28-mediated heterochromatin formation in immortalized cells.

The first author is Tsai Chia-Tsen, a PhD student in the TIGP-MCB program at Academia Sinica. The research was supported by the Academia Sinica Grand Challenge Program and the NSTC. This study was published on March 31, 2026, in The EMBO Journal.