Steroid receptors reprogram FoxA1 occupancy through dynamic chromatin transitions

Erin E Swinstead, Tina B Miranda, Ville Paakinaho, Songjoon Baek, Ido Goldstein, Mary Hawkins, Tatiana S Karpova, David Ball, Davide Mazza, Luke D Lavis, Jonathan B Grimm, Tatsuya Morisaki, Lars Grøntved, Diego M Presman, Gordon L Hager

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Abstrakt

The estrogen receptor (ER), glucocorticoid receptor (GR), and forkhead box protein 1 (FoxA1) are significant factors in breast cancer progression. FoxA1 has been implicated in establishing ER-binding patterns though its unique ability to serve as a pioneer factor. However, the molecular interplay between ER, GR, and FoxA1 requires further investigation. Here we show that ER and GR both have the ability to alter the genomic distribution of the FoxA1 pioneer factor. Single-molecule tracking experiments in live cells reveal a highly dynamic interaction of FoxA1 with chromatin in vivo. Furthermore, the FoxA1 factor is not associated with detectable footprints at its binding sites throughout the genome. These findings support a model wherein interactions between transcription factors and pioneer factors are highly dynamic. Moreover, at a subset of genomic sites, the role of pioneer can be reversed, with the steroid receptors serving to enhance binding of FoxA1.

OriginalsprogEngelsk
TidsskriftCell
Vol/bind165
Udgave nummer3
Sider (fra-til)593-605
ISSN0092-8674
DOI
StatusUdgivet - 21. apr. 2016
Udgivet eksterntJa

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  • Citationsformater

    Swinstead, E. E., Miranda, T. B., Paakinaho, V., Baek, S., Goldstein, I., Hawkins, M., Karpova, T. S., Ball, D., Mazza, D., Lavis, L. D., Grimm, J. B., Morisaki, T., Grøntved, L., Presman, D. M., & Hager, G. L. (2016). Steroid receptors reprogram FoxA1 occupancy through dynamic chromatin transitions. Cell, 165(3), 593-605. https://doi.org/10.1016/j.cell.2016.02.067