title: Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions.
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.
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Swinstead
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Tina B
authors.initials: TB
authors.lastname: Miranda
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Ville
authors.initials: V
authors.lastname: Paakinaho
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Songjoon
authors.initials: S
authors.lastname: Baek
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Ido
authors.initials: I
authors.lastname: Goldstein
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Hawkins
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Karpova
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ball
authors.affiliation: Istituto Scientifico Ospedale San Raffaele, Centro di Imaging Sperimentale e Università Vita-Salute San Raffaele, 20132 Milano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Mazza
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Luke D
authors.initials: LD
authors.lastname: Lavis
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Grimm
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morisaki
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Grøntved
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Presman
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Building 41, 41 Library Drive, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: hagerg@exchange.nih.gov.
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Hager
mesh_terms: D002843:Chromatin / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D011960:Receptors, Estrogen / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D003851:Deoxyribonucleases