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

doi:10.1016/j.cell.2016.02.067

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

222 Scopus citations

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	English
Pages (from-to)	593-605
Number of pages	13
Journal	Cell
Volume	165
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2016.02.067
State	Published - 21 Apr 2016
Externally published	Yes

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Publisher Copyright:
© 2016 Elsevier Inc.

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10.1016/j.cell.2016.02.067

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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.",

author = "Swinstead, {Erin E.} and Miranda, {Tina B.} and Ville Paakinaho and Songjoon Baek and Ido Goldstein and Mary Hawkins and Karpova, {Tatiana S.} and David Ball and Davide Mazza and Lavis, {Luke D.} and Grimm, {Jonathan B.} and Tatsuya Morisaki and Lars Gr{\o}ntved and Presman, {Diego M.} and Hager, {Gordon L.}",

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doi = "10.1016/j.cell.2016.02.067",

language = "אנגלית",

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AU - Swinstead, Erin E.

AU - Miranda, Tina B.

AU - Paakinaho, Ville

AU - Baek, Songjoon

AU - Goldstein, Ido

AU - Hawkins, Mary

AU - Karpova, Tatiana S.

AU - Ball, David

AU - Mazza, Davide

AU - Lavis, Luke D.

AU - Grimm, Jonathan B.

AU - Morisaki, Tatsuya

AU - Grøntved, Lars

AU - Presman, Diego M.

AU - Hager, Gordon L.

PY - 2016/4/21

Y1 - 2016/4/21

N2 - 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.

AB - 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.

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Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions

Abstract

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