IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-11378-4.html
   My bibliography  Save this article

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

Author

Listed:
  • Mohamed Osama Ali Abdalla

    (Kumamoto University
    Suez Canal University)

  • Tatsuro Yamamoto

    (Kumamoto University
    The Cancer Institute of JFCR
    Kumamoto University)

  • Kazumitsu Maehara

    (Kyushu University)

  • Jumpei Nogami

    (Kyushu University)

  • Yasuyuki Ohkawa

    (Kyushu University)

  • Hisashi Miura

    (RIKEN Center for Biosystems Dynamics Research (BDR))

  • Rawin Poonperm

    (RIKEN Center for Biosystems Dynamics Research (BDR))

  • Ichiro Hiratani

    (RIKEN Center for Biosystems Dynamics Research (BDR))

  • Hideki Nakayama

    (Kumamoto University)

  • Mitsuyoshi Nakao

    (Kumamoto University
    Japan Science and Technology Agency)

  • Noriko Saitoh

    (Kumamoto University
    The Cancer Institute of JFCR)

Abstract

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.

Suggested Citation

  • Mohamed Osama Ali Abdalla & Tatsuro Yamamoto & Kazumitsu Maehara & Jumpei Nogami & Yasuyuki Ohkawa & Hisashi Miura & Rawin Poonperm & Ichiro Hiratani & Hideki Nakayama & Mitsuyoshi Nakao & Noriko Sait, 2019. "The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11378-4
    DOI: 10.1038/s41467-019-11378-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-11378-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-11378-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11378-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.