YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation

  1. Lizhi He
  2. Henry Pratt
  3. Mingshi Gao
  4. Fengxiang Wei
  5. Zhiping Weng
  6. Kevin Struhl  Is a corresponding author
  1. Harvard Medical School, United States
  2. University of Massachusetts Medical School, United States
  3. Shenzhen Longgang District Maternity and Child Healthcare Hospital, China

Abstract

The YAP and TAZ paralogs are transcriptional co-activators recruited to target sites by TEAD proteins. Here, we show that YAP and TAZ are also recruited by JUNB (a member of the AP-1 family) and STAT3, key transcription factors that mediate an epigenetic switch linking inflammation to cellular transformation. YAP and TAZ directly interact with JUNB and STAT3 via a WW domain important for transformation, and they stimulate transcriptional activation by AP-1 proteins. JUNB, STAT3, and TEAD co-localize at virtually all YAP/TAZ target sites, yet many target sites only contain individual AP-1, TEAD, or STAT3 motifs. This observation and differences in relative crosslinking efficiencies of JUNB, TEAD, and STAT3 at YAP/TAZ target sites suggest that YAP/TAZ is recruited by different forms of an AP-1/STAT3/TEAD complex depending on the recruiting motif. The different classes of YAP/TAZ target sites are associated with largely non-overlapping genes with distinct functions. A small minority of target sites are YAP- or TAZ-specific, and they are associated with different sequence motifs and gene classes from shared YAP/TAZ target sites. Genes containing either the AP-1 or TEAD class of YAP/TAZ sites are associated with poor survival of breast cancer patients with the triple-negative form of the disease.

Data availability

All sequencing data were deposited on National Cancer for Biotechnology Information Gene Expression Omnibus (GEO). GSE166943 is the accession number for all the data, with GSE166941 being the subset for the ChIP-seq data and GSE166942 for the RNA-seq data.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Lizhi He

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8571-3656
  2. Henry Pratt

    Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
  3. Mingshi Gao

    Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7524-892X
  4. Fengxiang Wei

    Genetics Laboratory, Shenzhen Longgang District Maternity and Child Healthcare Hospital, Shenzhen, China
    Competing interests
    No competing interests declared.
  5. Zhiping Weng

    Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3032-7966
  6. Kevin Struhl

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    For correspondence
    kevin@hms.harvard.edu
    Competing interests
    Kevin Struhl, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4181-7856

Funding

National Cancer Institute (GM 107486)

  • Kevin Struhl

National Institutes of Health (HG009486)

  • Zhiping Weng

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jessica K Tyler, Weill Cornell Medicine, United States

Version history

  1. Received: February 7, 2021
  2. Preprint posted: February 18, 2021 (view preprint)
  3. Accepted: August 26, 2021
  4. Accepted Manuscript published: August 31, 2021 (version 1)
  5. Version of Record published: September 24, 2021 (version 2)

Copyright

© 2021, He et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lizhi He
  2. Henry Pratt
  3. Mingshi Gao
  4. Fengxiang Wei
  5. Zhiping Weng
  6. Kevin Struhl
(2021)
YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation
eLife 10:e67312.
https://doi.org/10.7554/eLife.67312

Share this article

https://doi.org/10.7554/eLife.67312

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