Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer.

Autor:	Achinger-Kawecka J; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, 2010, Australia., Valdes-Mora F; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, 2010, Australia., Luu PL; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, 2010, Australia., Giles KA; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Caldon CE; Cancer Theme, The Kinghorn Cancer Centre, Sydney, NSW, 2010, Australia., Qu W; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Nair S; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Soto S; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Locke WJ; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Yeo-Teh NS; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Gould CM; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Du Q; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Smith GC; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia., Ramos IR; Department of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA, USA., Fernandez KF; Cancer Theme, The Kinghorn Cancer Centre, Sydney, NSW, 2010, Australia., Hoon DS; Department of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA, USA., Gee JMW; Breast Cancer Molecular Pharmacology Group, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Wales, CF10 3NB, UK., Stirzaker C; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, 2010, Australia., Clark SJ; Epigenetics Research Laboratory, Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia. s.clark@garvan.org.au.; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, 2010, Australia. s.clark@garvan.org.au.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Jan 16; Vol. 11 (1), pp. 320. Date of Electronic Publication: 2020 Jan 16.
DOI:	10.1038/s41467-019-14098-x
Abstrakt:	Endocrine therapy resistance frequently develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine-resistant breast cancer cells and that the differential interactions are enriched for resistance-associated genetic variants at CTCF-bound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites, and are associated with altered expression of ER-regulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. We observe that loss of 3D chromatin interactions often occurs coincidently with hypermethylation and loss of ER binding. Alterations in active A and inactive B chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer.
Databáze:	MEDLINE
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