Telomeres are crucial for maintaining chromosomal integrity and are characterized by repetitive DNA sequences, which may be stabilized by the shelterin protein complex or by formation of secondary structures, such as G-quadruplexes (G4 DNA). Frequently, subtelomeric regions are decorated with di- and tri-methylated lysine 27 on histone H3 (H3K27me), repressive marks catalyzed by Polycomb Repressive Complex 2 that are associated with facultative heterochromatin in many eukaryotes. Our previous work with the filamentous fungus Neurospora crassa demonstrated that native telomere repeats induce H3K27me at ectopic loci. Here we report investigations into the mechanism of this and demonstrate that some non-native telomere repeats can also induce H3K27me. Hi-C analyses demonstrated that ectopic telomeric repeats can interact with native telomeres. Chromatin immunoprecipitation (ChIP) experiments with an anti-G4-DNA antibody showed that establishment of H3K27me was not correlated with the presence of G4 DNA. Other ChIP experiments demonstrated that the telomere repeat-binding protein TRF-1, which has been demonstrated to be a member of the shelterin complex in other systems, binds to interstitial telomere repeats that induce H3K27me. Tethering experiments revealed that TRF-1 binding is sufficient to induce H3K27me. Together these results suggest that TRF-1 plays a crucial role in establishment of H3K27me, and thus repression, at telomere sequences.
Mumford et al. (Tue,) studied this question.