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Local heterochromatin enrichment promotes telomere clustering and PML nuclear body assembly at telomeres.

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Cell reports 📖 저널 OA 47.5% 2022: 1/1 OA 2024: 6/12 OA 2025: 20/55 OA 2026: 31/54 OA 2022~2026 2026 Vol.45(3) p. 117004 OA
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Taylor ER, Proctor B, Vaurs M, Wu G, Mahieu M, Shrestha S

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The alternative lengthening of telomeres (ALT) pathway is a recombination-based telomere maintenance mechanism used by a subset of human cancers and is characterized by telomere clustering within telo

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APA Taylor ER, Proctor B, et al. (2026). Local heterochromatin enrichment promotes telomere clustering and PML nuclear body assembly at telomeres.. Cell reports, 45(3), 117004. https://doi.org/10.1016/j.celrep.2026.117004
MLA Taylor ER, et al.. "Local heterochromatin enrichment promotes telomere clustering and PML nuclear body assembly at telomeres.." Cell reports, vol. 45, no. 3, 2026, pp. 117004.
PMID 41712379 ↗

Abstract

The alternative lengthening of telomeres (ALT) pathway is a recombination-based telomere maintenance mechanism used by a subset of human cancers and is characterized by telomere clustering within telomere-associated promyelocytic leukemia (PML) nuclear bodies (APBs). Although ALT telomeres exhibit reduced nucleosome density, they are paradoxically enriched for heterochromatin-associated factors, raising questions about how chromatin state contributes to ALT. Here, we use a targeted system to locally modulate heterochromatin features at telomeres. We show that telomeric heterochromatin promotes telomere clustering and multiple hallmarks of APB-associated telomere processing in ALT-positive (ALT+) cells. Remarkably, molecular tethering of HP1α at telomeres is sufficient to nucleate PML nuclear bodies in non-ALT cells and, in specific contexts, induce biomarkers of ALT-like recombination. We further demonstrate that heterochromatin-driven PML-telomere colocalization is inhibited by α-thalassemia/mental retardation, X-linked and death domain-associated protein (ATRX/DAXX), factors frequently mutated in ALT+ tumors. Together, these findings establish telomeric heterochromatin as a driver of telomere clustering and PML nuclear body assembly, shaping ALT-associated subnuclear compartmentalization.

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