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Comprehensive Genomic Analysis Reveals that the Pioneering Function of FOXA1 Is Independent of Hormonal Signaling.

Authors
  • Glont, Silvia-E1
  • Chernukhin, Igor1
  • Carroll, Jason S2
  • 1 Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 ORE, UK.
  • 2 Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 ORE, UK. Electronic address: [email protected]
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Mar 05, 2019
Volume
26
Issue
10
Identifiers
DOI: 10.1016/j.celrep.2019.02.036
PMID: 30840881
Source
Medline
Language
English
License
Unknown

Abstract

Considerable work has linked hormone receptors, such as estrogen receptor-alpha (ER), with the pioneer factor FOXA1. Altered FOXA1 levels contribute to endocrine-resistant breast cancer, where it maintains ER-chromatin interactions, even in contexts in which cells are refractory to ER-targeted drugs. A recent study controversially suggests that FOXA1 binding can be induced by hormonal pathways, including the estrogen-ER complex. We now show that the vast majority (>99%) of FOXA1 binding events are unaffected by steroid activation. A small number (<1%) of FOXA1 binding sites appear to be induced by estrogen, but these are created from chromatin interactions between ER binding sites and adjacent FOXA1 binding sites and do not represent genuine new FOXA1-pioneering elements. FOXA1 is therefore not regulated by estrogen and remains a bone fide pioneer factor that is entirely upstream of the ER complex. Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

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