A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation

Saori Tomita, Mohamed Osama Ali Abdalla, Saori Fujiwara, Haruka Matsumori, Kazumitsu Maehara, Yasuyuki Ohkawa, Hirotaka Iwase, Noriko Saitoh, Mitsuyoshi Nakao

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Estrogen receptor-α (ER)-positive breast cancer cells undergo hormone-independent proliferation after deprivation of oestrogen, leading to endocrine therapy resistance. Up-regulation of the ER gene (ESR1) is critical for this process, but the underlying mechanisms remain unclear. Here we show that the combination of transcriptome and fluorescence in situ hybridization analyses revealed that oestrogen deprivation induced a cluster of noncoding RNAs that defined a large chromatin domain containing the ESR1 locus. We termed these RNAs as Eleanors (ESR1 locus enhancing and activating noncoding RNAs). Eleanors were present in ER-positive breast cancer tissues and localized at the transcriptionally active ESR1 locus to form RNA foci. Depletion of one Eleanor, upstream (u)-Eleanor, impaired cell growth and transcription of intragenic Eleanors and ESR1 mRNA, indicating that Eleanors cis-activate the ESR1 gene. Eleanor-mediated gene activation represents a new type of locus control mechanism and plays an essential role in the adaptation of breast cancer cells.

Original languageEnglish
Article number6966
JournalNature communications
Volume6
DOIs
Publication statusPublished - Apr 29 2015

Fingerprint

Untranslated RNA
loci
breast
estrogens
cancer
Breast Neoplasms
Estrogen Receptors
Genes
genes
deprivation
Estrogens
Cells
RNA
Internal-External Control
Cell growth
Transcription
Fluorescence In Situ Hybridization
Transcriptome
Transcriptional Activation
Chromatin

All Science Journal Classification (ASJC) codes

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

Cite this

A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation. / Tomita, Saori; Abdalla, Mohamed Osama Ali; Fujiwara, Saori; Matsumori, Haruka; Maehara, Kazumitsu; Ohkawa, Yasuyuki; Iwase, Hirotaka; Saitoh, Noriko; Nakao, Mitsuyoshi.

In: Nature communications, Vol. 6, 6966, 29.04.2015.

Research output: Contribution to journalArticle

Tomita, S, Abdalla, MOA, Fujiwara, S, Matsumori, H, Maehara, K, Ohkawa, Y, Iwase, H, Saitoh, N & Nakao, M 2015, 'A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation', Nature communications, vol. 6, 6966. https://doi.org/10.1038/ncomms7966
Tomita, Saori ; Abdalla, Mohamed Osama Ali ; Fujiwara, Saori ; Matsumori, Haruka ; Maehara, Kazumitsu ; Ohkawa, Yasuyuki ; Iwase, Hirotaka ; Saitoh, Noriko ; Nakao, Mitsuyoshi. / A cluster of noncoding RNAs activates the ESR1 locus during breast cancer adaptation. In: Nature communications. 2015 ; Vol. 6.
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AU - Iwase, Hirotaka

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