| Literature DB >> 28781121 |
Gulfem Dilek Guler1, Charles Albert Tindell1, Robert Pitti1, Catherine Wilson1, Katrina Nichols2, Tommy KaiWai Cheung2, Hyo-Jin Kim1, Matthew Wongchenko3, Yibing Yan3, Benjamin Haley4, Trinna Cuellar4, Joshua Webster5, Navneet Alag1, Ganapati Hegde1, Erica Jackson1, Tracy Leah Nance6, Paul Garrett Giresi6, Kuan-Bei Chen7, Jinfeng Liu8, Suchit Jhunjhunwala8, Jeff Settleman1, Jean-Philippe Stephan2, David Arnott2, Marie Classon9.
Abstract
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.Entities:
Keywords: ATRX; G9a; H3.3; H3K9-methylation; HDACs; HP1γ; LINE-1; SETDB1; cancer cell heterogeneity; chromatin
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Year: 2017 PMID： 28781121 DOI： 10.1016/j.ccell.2017.07.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743