IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-25670-9.html
   My bibliography  Save this article

Genetic variations of DNA bindings of FOXA1 and co-factors in breast cancer susceptibility

Author

Listed:
  • Wanqing Wen

    (Vanderbilt University Medical Center)

  • Zhishan Chen

    (Vanderbilt University Medical Center)

  • Jiandong Bao

    (Fujian Agriculture and Forestry University)

  • Quan Long

    (O’Brien Institute for Public Health)

  • Xiao-ou Shu

    (Vanderbilt University Medical Center)

  • Wei Zheng

    (Vanderbilt University Medical Center)

  • Xingyi Guo

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

Abstract

Identifying transcription factors (TFs) whose DNA bindings are altered by genetic variants that regulate susceptibility genes is imperative to understand transcriptional dysregulation in disease etiology. Here, we develop a statistical framework to analyze extensive ChIP-seq and GWAS data and identify 22 breast cancer risk-associated TFs. We find that, by analyzing genetic variations of TF-DNA bindings, the interaction of FOXA1 with co-factors such as ESR1 and E2F1, and the interaction of TFs with chromatin features (i.e., enhancers) play a key role in breast cancer susceptibility. Using genetic variants occupied by the 22 TFs, transcriptome-wide association analyses identify 52 previously unreported breast cancer susceptibility genes, including seven with evidence of essentiality from functional screens in breast relevant cell lines. We show that FOXA1 and co-factors form a core TF-transcriptional network regulating the susceptibility genes. Our findings provide additional insights into genetic variations of TF-DNA bindings (particularly for FOXA1) underlying breast cancer susceptibility.

Suggested Citation

  • Wanqing Wen & Zhishan Chen & Jiandong Bao & Quan Long & Xiao-ou Shu & Wei Zheng & Xingyi Guo, 2021. "Genetic variations of DNA bindings of FOXA1 and co-factors in breast cancer susceptibility," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25670-9
    DOI: 10.1038/s41467-021-25670-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-25670-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-25670-9?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jingni He & Wanqing Wen & Alicia Beeghly & Zhishan Chen & Chen Cao & Xiao-Ou Shu & Wei Zheng & Quan Long & Xingyi Guo, 2022. "Integrating transcription factor occupancy with transcriptome-wide association analysis identifies susceptibility genes in human cancers," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    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:12:y:2021:i:1:d:10.1038_s41467-021-25670-9. 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.