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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Glont, Silvia-E 
Chernukhin, Igor 
Carroll, Jason S 

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.

Description

Keywords

Animals, Cell Line, Genomics, Hepatocyte Nuclear Factor 3-alpha, Humans, MCF-7 Cells, Rabbits, Signal Transduction

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

26

Publisher

Elsevier BV
Sponsorship
European Research Council (646876)
Cancer Research UK (C14303/A17197)
Susan G Komen Breast Cancer Foundation (SAC160065)
ERC Consolidator award (Project number 646876), CRUK funding and a Komen Scholarship.