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Steroid Receptors can Activate Unique FoxA1 Binding Patterns through a Highly Dynamic Mechanism Associated with a Fast DNA Residence Time
Author(s) -
Swinstead Erin E,
Miranda Tina B,
Paakinaho Ville,
Baek Soongjoon,
Hawkins Mary,
Karpova Tatiana,
Ball David,
Mazza Davide,
Lavis Luke D,
Morisaki Tatsuya,
Grøntved Lars,
Presman Diego M,
Hager Gordon L
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.585.5
Subject(s) - foxa1 , chromatin , transcription factor , microbiology and biotechnology , biology , chemistry , genetics , dna , gene
The transcription factor (TF) FoxA1 has been implicated in steroid receptor (SR) binding patterns serving as a pioneer factor; however, the effects of SRs on the function of FoxA1 have been controversial. Classically it has been proposed that FoxA1 has a slow residence time on DNA allowing chromatin to remain open permitting access of SRs to binding sites. Conversely, it has recently been identified that SRs can alter the binding landscape of each other facilitating selective access to the chromatin by a mechanism termed dynamic assisted loading. To determine if this phenomenon extends to FoxA1 we characterised the estrogen receptor (ER), glucocorticoid receptor (GR), and FoxA1 in three breast cancer cell lines. Genome‐wide analysis of ChIP and DNaseI hypersensitivity assays upon hormone treatment show that both SRs can recruit FoxA1 to specific binding sites associated with an increase in chromatin accessibility. This indicates chromatin reorganization upon activation of ER and GR and recruitment of FoxA1 binding through an assisted loading mechanism. Most importantly, we have established the DNA residence time of FoxA1 by single‐molecule tracking in living cell at a rate of ~8–10 seconds. This finding is supported by the lack of a detectable FoxA1 DNase footprint together indicating fast chromatin interactions. These results suggest that many TFs in a given cell have the potential to affect the binding landscape of other TFs, depending on the chromatin context. In addition, this study has shifted our classical understanding of pioneer factors in breast cancer, demonstrating that steroid receptors can alter the response of FoxA1 though highly dynamic and fast DNA interactions. Support or Funding Information This research was supported by grants from the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.