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Cell. 2016 Apr 21;165(3):593-605. doi: 10.1016/j.cell.2016.02.067. Epub 2016 Apr 7.

Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions.

Author information

1
Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
2
Istituto Scientifico Ospedale San Raffaele, Centro di Imaging Sperimentale e Università Vita-Salute San Raffaele, 20132 Milano, Italy.
3
Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
4
Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: hagerg@exchange.nih.gov.

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.

PMID:
27062924
PMCID:
PMC4842147
DOI:
10.1016/j.cell.2016.02.067
[Indexed for MEDLINE]
Free PMC Article

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