FOXA1 acts upstream of GATA2 and AR in hormonal regulation of gene expression

J. C. Zhao, K. W. Fong, H. J. Jin, Y. A. Yang, J. Kim, J. Yu

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Hormonal regulation of gene expression by androgen receptor (AR) is tightly controlled by many transcriptional cofactors, including pioneer factors FOXA1 and GATA2, which, however, exhibit distinct expression patterns and functional roles in prostate cancer. Here, we examined how FOXA1, GATA2 and AR crosstalk and regulate hormone-dependent gene expression in prostate cancer cells. Chromatin immunoprecipitation sequencing analysis revealed that FOXA1 reprograms both AR and GATA2 cistrome by preferably recruiting them to FKHD-containing genomic sites. By contrast, GATA2 is unable to shift AR or FOXA1 to GATA motifs. Rather, GATA2 co-occupancy enhances AR and FOXA1 binding to nearby ARE and FKHD sites, respectively. Similarly, AR increases, but not reprograms, GATA2 and FOXA1 cistromes. Concordantly, GATA2 and AR strongly enhance the transcriptional program of each other, whereas FOXA1 regulates GATA2- and AR-mediated gene expression in a context-dependent manner due to its reprogramming effects. Taken together, our data delineated for the first time the distinct mechanisms by which GATA2 and FOXA1 regulate AR cistrome and suggest that FOXA1 acts upstream of GATA2 and AR in determining hormone-dependent gene expression in prostate cancer.

Original languageEnglish
Pages (from-to)4335-4344
Number of pages10
JournalOncogene
Volume35
Issue number33
DOIs
StatePublished - Aug 18 2016

Bibliographical note

Publisher Copyright:
© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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