A Rapid, Extensive, and Transient Transcriptional Response to Estrogen Signaling in Breast Cancer Cells

SummaryWe report the immediate effects of estrogen signaling on the transcriptome of breast cancer cells using global run-on and sequencing (GRO-seq). The data were analyzed using a new bioinformatic approach that allowed us to identify transcripts directly from the GRO-seq data. We found that estrogen signaling directly regulates a strikingly large fraction of the transcriptome in a rapid, robust, and unexpectedly transient manner. In addition to protein-coding genes, estrogen regulates the distribution and activity of all three RNA polymerases and virtually every class of noncoding RNA that has been described to date. We also identified a large number of previously undetected estrogen-regulated intergenic transcripts, many of which are found proximal to estrogen receptor binding sites. Collectively, our results provide the most comprehensive measurement of the primary and immediate estrogen effects to date and a resource for understanding rapid signal-dependent transcription in other systems.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (292 K)Download as PowerPoint slideHighlights► Global run-on sequencing shows immediate transcriptional effects of estrogen signaling ► Estrogen regulates 25% of the breast cancer transcriptome rapidly and transiently ► Estrogen regulates the production of all classes of coding and noncoding transcripts ► Estrogen regulates the production of many as yet unannotated intergenic transcripts