Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions

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 be...

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Detalles Bibliográficos
Autores: Swinstead, Erin E., Miranda, Tina B., Paakinaho, Ville, Baek, Songjoon, Goldstein, Ido, Hawkins, Mary, Karpova, Tatiana S., Ball, David, Mazza, Davide, Lavis, Luke D., Grimm, Jonathan B., Morisaki, Tatsuya, Grøntved, Lars, Presman, Diego Martin, Hager, Gordon L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/60625
Acceso en línea:http://hdl.handle.net/11336/60625
Access Level:acceso abierto
Palabra clave:Foxa1
Chromatin
Single Molecule Tracking
Glucocorticoid Receptor
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario: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.