Abstract
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.
| Original language | American English |
|---|---|
| Pages (from-to) | 593-605 |
| Number of pages | 13 |
| Journal | Cell |
| Volume | 165 |
| Issue number | 3 |
| DOIs | |
| State | Published - 21 Apr 2016 |
| Externally published | Yes |
Bibliographical note
Funding Information:The authors thank the National Cancer Institute Advanced Technology Program Sequencing Facility for sequencing services. The research was supported, in part, by the Intramural Research Program of the NIH, NCI, Center for Cancer Research and the Howard Hughes Medical Institute. E.E.S. was supported, in part, by an Australian Postgraduate Award. T.B.M. was supported, in part, by a National Institute of General Medical Sciences Pharmacological Research and Training Fellowship. V.P. was supported, in part, by the Sigrid Jus?lius Foundation. D.M. was supported, in part, by a Marie Curie International Incoming Fellowship (GA: 27432). T.M. was supported, in part, by the Japan Society for the Promotion of Science. L.G. was supported by the Danish Research Council and SDU2020. The authors declare the following competing financial interests: J.B.G. and L.D.L. have filed patent applications on the Janelia Fluor dyes, such as JF549, whose value may be affected by this publication.
Funding Information:
The authors thank the National Cancer Institute Advanced Technology Program Sequencing Facility for sequencing services. The research was supported, in part, by the Intramural Research Program of the NIH, NCI, Center for Cancer Research and the Howard Hughes Medical Institute. E.E.S. was supported, in part, by an Australian Postgraduate Award. T.B.M. was supported, in part, by a National Institute of General Medical Sciences Pharmacological Research and Training Fellowship. V.P. was supported, in part, by the Sigrid Jusélius Foundation. D.M. was supported, in part, by a Marie Curie International Incoming Fellowship (GA: 27432). T.M. was supported, in part, by the Japan Society for the Promotion of Science. L.G. was supported by the Danish Research Council and SDU2020. The authors declare the following competing financial interests: J.B.G. and L.D.L. have filed patent applications on the Janelia Fluor dyes, such as JF549, whose value may be affected by this publication.
Publisher Copyright:
© 2016 Elsevier Inc.
