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The Estrogen-Regulated Transcriptome: Rapid, Robust, Extensive, and Transient

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Estrogen Receptor and Breast Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The steroid hormone estrogen has potent effects in a variety of tissues across the body in both females and males. In the nuclear signaling pathway for estrogens, the hormone acts by stimulating the DNA binding and transcriptional activity of estrogen receptors (ERs), transcription factors which robustly and transiently regulate the expression of target genes. More broadly, estrogen signaling controls the ER cistrome, as well as the epigenome and the estrogen-regulated transcriptome. A host of deep sequencing-based genomic assays have provided novel insights into the mechanisms by which ERs regulate transcriptional responses. Estrogen-dependent transcriptional responses have been studied widely in breast cancer cells, primarily in the context of the ER alpha (ERα) isoform. These studies have revealed an intricate cross talk between the estrogen-ERα signaling pathway and other signaling pathways, impacting transcriptional programs and clinical outcomes in breast cancer. This chapter reviews the key features of ERα-regulated transcription and the current technological advances that have allowed for the careful dissection of these mechanisms.

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Acknowledgments

We are grateful for critical comments and suggestions from members of the Kraus lab, including Shino Murakami, Anusha Nagari, and J. Tyler Piazza. We are also thankful for the contributions of past Kraus lab members, whose studies furthering our understanding of the molecular mechanisms of estrogen-regulated transcription are highlighted in this review, including Nasun Hah, Charles Danko, Shino Murakami, Hector Franco, and Anusha Nagari. The estrogen-related studies in the Kraus lab are supported by grants from the NIH/NIDDK and the Cancer Prevention and Research Institute of Texas (CPRIT) to W.L.K. Y.M.V. is supported by a Postdoctoral Research Fellowship from the Lalor Foundation.

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  1. Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Yasmin M. Vasquez & W. Lee Kraus

  2. Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Yasmin M. Vasquez & W. Lee Kraus

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  1. Department of Cancer Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Xiaoting Zhang

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Vasquez, Y.M., Kraus, W.L. (2019). The Estrogen-Regulated Transcriptome: Rapid, Robust, Extensive, and Transient. In: Zhang, X. (eds) Estrogen Receptor and Breast Cancer. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-99350-8_5

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