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Hormone-regulated transcriptomes: Lessons learned from estrogen signaling pathways in breast cancer cells

Nasun Hah; W. Lee Kraus

(Profiled Author: William L Kraus)

Molecular and Cellular Endocrinology. 2014;382(1):652-664.

Abstract

Recent rapid advances in next generation sequencing technologies have expanded our understanding of steroid hormone signaling to a genome-wide level. In this review, we discuss the use of a novel genomic approach, global nuclear run-. on coupled with massively parallel sequencing (GRO-seq), to explore new facets of the steroid hormone-regulated transcriptome, especially estrogen responses in breast cancer cells. GRO-seq is a high throughput sequencing method adapted from conventional nuclear run-on methodologies, which is used to obtain a map of the position and orientation of all transcriptionally engaged RNA polymerases across the genome with extremely high spatial resolution. GRO-seq, which is an excellent tool for examining transcriptional responses to extracellular stimuli, has been used to comprehensively assay the effects of estrogen signaling on the transcriptome of ERα-positive MCF-7 human breast cancer cells. These studies have revealed new details about estrogen-dependent transcriptional regulation, including effects on transcription by all three RNA polymerases, complex transcriptional dynamics in response to estrogen signaling, and identification novel, unannotated non-coding RNAs. Collectively, these studies have been useful in discerning the molecular logic of the estrogen-regulated mitogenic response. © 2013 Elsevier Ireland Ltd.

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