The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis

Mohamed Osama Ali Abdalla, Tatsuro Yamamoto, Kazumitsu Maehara, Jumpei Nogami, Yasuyuki Ohkawa, Hisashi Miura, Rawin Poonperm, Ichiro Hiratani, Hideki Nakayama, Mitsuyoshi Nakao, Noriko Saitoh

研究成果: Contribution to journalArticle

6 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号3778
ジャーナルNature communications
10
1
DOI
出版ステータス出版済み - 12 1 2019

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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