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Genome-wide Estrogen Receptor-α activation is sustained, not cyclical

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Genome-wide Estrogen Receptor-α activation is sustained, not cyclical. / Holding, A; Cullen, A; Markowetz, F.

In: eLife, Vol. 7, e40854, 20.11.2018.

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Harvard

Holding, A, Cullen, A & Markowetz, F 2018, 'Genome-wide Estrogen Receptor-α activation is sustained, not cyclical', eLife, vol. 7, e40854. https://doi.org/10.7554/eLife.40854

APA

Holding, A., Cullen, A., & Markowetz, F. (2018). Genome-wide Estrogen Receptor-α activation is sustained, not cyclical. eLife, 7, [e40854]. https://doi.org/10.7554/eLife.40854

Vancouver

Holding A, Cullen A, Markowetz F. Genome-wide Estrogen Receptor-α activation is sustained, not cyclical. eLife. 2018 Nov 20;7. e40854. https://doi.org/10.7554/eLife.40854

Author

Holding, A ; Cullen, A ; Markowetz, F. / Genome-wide Estrogen Receptor-α activation is sustained, not cyclical. In: eLife. 2018 ; Vol. 7.

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@article{61abc25757e24c38bdf4df7833f2e502,
title = "Genome-wide Estrogen Receptor-α activation is sustained, not cyclical",
abstract = "Abstract Estrogen Receptor- α (ER) is the key driver of 75% of all breast cancers. Upon stimulation by its ligand estra-2-diol, ER forms a transcriptionally active complex binding chromatin. Previous studies have reported that ER binding follows a cyclical binding pattern with a periodicity of 90 minutes. However, these studies have been limited to individual ER target genes and most were done without replicates. Thus, the robustness and generality of ER cycling are not well understood. Here we present a comprehensive genome-wide analysis of the time dependence of ER binding affinity up to 90 minutes after activation, based on 6 replicates at 10 time points using our previously reported method for precise quantification of binding, Parallel-Factor ChIP-seq (pfChIP-seq). In contrast to previously described cyclical binding, our approach identifies a unidirectional sustained increase in ER binding affinity, as well as a class of estra-2-diol independent binding sites. Our results are corrob-orated by a quantitative re-analysis of data from multiple independent studies. Our new model reconciles the results of multiple conflicting studies into the activation of ER at the TFF1 promoter. We provide a detailed understanding of ER{\textquoteright}s response to estra-2-diol in the context of the receptor{\textquoteright}s fundamental role as both the main driver and therapeutic target of breast cancer.",
author = "A Holding and A Cullen and F Markowetz",
note = "{\textcopyright} 2019, The Author(s). ",
year = "2018",
month = nov,
day = "20",
doi = "10.7554/eLife.40854",
language = "English",
volume = "7",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Genome-wide Estrogen Receptor-α activation is sustained, not cyclical

AU - Holding, A

AU - Cullen, A

AU - Markowetz, F

N1 - © 2019, The Author(s).

PY - 2018/11/20

Y1 - 2018/11/20

N2 - Abstract Estrogen Receptor- α (ER) is the key driver of 75% of all breast cancers. Upon stimulation by its ligand estra-2-diol, ER forms a transcriptionally active complex binding chromatin. Previous studies have reported that ER binding follows a cyclical binding pattern with a periodicity of 90 minutes. However, these studies have been limited to individual ER target genes and most were done without replicates. Thus, the robustness and generality of ER cycling are not well understood. Here we present a comprehensive genome-wide analysis of the time dependence of ER binding affinity up to 90 minutes after activation, based on 6 replicates at 10 time points using our previously reported method for precise quantification of binding, Parallel-Factor ChIP-seq (pfChIP-seq). In contrast to previously described cyclical binding, our approach identifies a unidirectional sustained increase in ER binding affinity, as well as a class of estra-2-diol independent binding sites. Our results are corrob-orated by a quantitative re-analysis of data from multiple independent studies. Our new model reconciles the results of multiple conflicting studies into the activation of ER at the TFF1 promoter. We provide a detailed understanding of ER’s response to estra-2-diol in the context of the receptor’s fundamental role as both the main driver and therapeutic target of breast cancer.

AB - Abstract Estrogen Receptor- α (ER) is the key driver of 75% of all breast cancers. Upon stimulation by its ligand estra-2-diol, ER forms a transcriptionally active complex binding chromatin. Previous studies have reported that ER binding follows a cyclical binding pattern with a periodicity of 90 minutes. However, these studies have been limited to individual ER target genes and most were done without replicates. Thus, the robustness and generality of ER cycling are not well understood. Here we present a comprehensive genome-wide analysis of the time dependence of ER binding affinity up to 90 minutes after activation, based on 6 replicates at 10 time points using our previously reported method for precise quantification of binding, Parallel-Factor ChIP-seq (pfChIP-seq). In contrast to previously described cyclical binding, our approach identifies a unidirectional sustained increase in ER binding affinity, as well as a class of estra-2-diol independent binding sites. Our results are corrob-orated by a quantitative re-analysis of data from multiple independent studies. Our new model reconciles the results of multiple conflicting studies into the activation of ER at the TFF1 promoter. We provide a detailed understanding of ER’s response to estra-2-diol in the context of the receptor’s fundamental role as both the main driver and therapeutic target of breast cancer.

U2 - 10.7554/eLife.40854

DO - 10.7554/eLife.40854

M3 - Article

VL - 7

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e40854

ER -