Maintenance of phenotypic heterogeneity within cell populations is an evolutionarily conserved mechanism that underlies population survival upon stressful exposures. We show that the genomes of a cancer cell subpopulation that survives treatment with otherwise lethal drugs, the drug-tolerant persisters (DTPs), exhibit a repressed chromatin state characterized by increased methylation of histone H3 lysines 9 and 27 (H3K9 and H3K27). We also show that survival of DTPs is, in part, maintained by regulators of H3K9me3-mediated heterochromatin formation and that the observed increase in H3K9me3 in DTPs is most prominent over long interspersed repeat element 1 (LINE-1). Disruption of the repressive chromatin over LINE-1 elements in DTPs results in DTP ablation, which is partially rescued by reducing LINE-1 expression or function.

中文翻译：

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抑制压力诱导的LINE-1表达可保护癌细胞亚群免于致死性药物暴露。

在细胞群体内维持表型异质性是一种进化保守的机制，该机制是压力暴露下群体存活的基础。我们显示癌细胞生存的癌细胞亚群的基因组，否则可以使用致命药，耐药性持久性物质（DTPs）来治疗，表现出抑制的染色质状态，其特征在于组蛋白H3赖氨酸9和27（H3K9和H3K27）的甲基化增加。我们还显示，DTP的存活在一定程度上由H3K9me3介导的异染色质形成的调节剂维持，并且观察到的DTP中H3K9me3的增加在长时间散布的重复元件1（LINE-1）上最为突出。DTP中LINE-1元件上抑制性染色质的破坏导致DTP消融，其通过降低LINE-1的表达或功能得以部分挽救。