Nature communications, 2019-08, Vol.10 (1), p.3778-15, Article 3778
2019
Details
- Autor(en) / Beteiligte
- Titel
- The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis
- Ist Teil von
- Nature communications, 2019-08, Vol.10 (1), p.3778-15, Article 3778
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- MCF7 cells acquire estrogen-independent proliferation after long-term estrogen deprivation (LTED), which recapitulates endocrine therapy resistance. LTED cells can become primed for apoptosis, but the underlying mechanism is largely unknown. We previously reported that Eleanor non-coding RNAs (ncRNAs) upregulate the ESR1 gene in LTED cells. Here, we show that Eleanors delineate the topologically associating domain (TAD) of the ESR1 locus in the active nuclear compartment of LTED cells. The TAD interacts with another transcriptionally active TAD, which is 42.9 Mb away from ESR1 and contains a gene encoding the apoptotic transcription factor FOXO3. Inhibition of a promoter-associated Eleanor suppresses all genes inside the Eleanor TAD and the long-range interaction between the two TADs, but keeps FOXO3 active to facilitate apoptosis in LTED cells. These data indicate a role of ncRNAs in chromatin domain regulation, which may underlie the apoptosis-prone nature of therapy-resistant breast cancer cells and could be good therapeutic targets.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-11378-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_942f290119a6494eac46f39607ac50db
- Format
- –
- Schlagworte
- Antineoplastic Agents, Hormonal - pharmacology, Antineoplastic Agents, Hormonal - therapeutic use, Apoptosis, Apoptosis - drug effects, Apoptosis - genetics, Aromatase Inhibitors - pharmacology, Aromatase Inhibitors - therapeutic use, Binding Sites - genetics, Breast cancer, Breast Neoplasms - drug therapy, Breast Neoplasms - genetics, Breast Neoplasms - pathology, Cell proliferation, Chromatin, Chromatin - genetics, Chromatin - metabolism, Deprivation, Drug Resistance, Neoplasm - genetics, Epigenesis, Genetic, Estrogen Receptor alpha - genetics, Estrogen Receptor alpha - metabolism, Estrogen receptors, Estrogens, Estrogens - metabolism, Female, Forkhead Box Protein O3 - genetics, Forkhead Box Protein O3 - metabolism, FOXO3 protein, Gene Expression Regulation, Neoplastic, Genetic Loci - genetics, High-Throughput Nucleotide Sequencing, Humans, Loci, MCF-7 Cells, Promoter Regions, Genetic - genetics, RNA, Untranslated - metabolism, Therapeutic applications, Therapy, Up-Regulation