Enhancer transcripts mark active estrogen receptor binding sites

• DOI: 10.1101/gr.152306.112
• Publication Date: 2013-05-02T08:58:08Z
• Authors: Nasun Hah; Shino Murakami; Anusha Nagari; Charles G. Danko; W. Lee Kraus
• Keywords: Enhancer RNAs; Estrogen receptor alpha; RNA polymerase II; Transcription

We have integrated and analyzed a large number of data sets from variety genomic assays using novel computational pipeline to provide global view estrogen receptor 1 (ESR1; a.k.a. ERα) enhancers in MCF-7 human breast cancer cells. Using this approach, we defined class primary transcripts (eRNAs) that are transcribed uni- or bidirectionally binding sites (ERBSs) with an average transcription unit length ∼3–5 kb. The majority up-regulated by short treatments estradiol (i.e., 10, 25, 40 min) kinetics precede match the induction target genes. production eRNAs at ERBSs is strongly correlated enrichment features associated (e.g., H3K4me1, H3K27ac, EP300/CREBBP, RNA polymerase II, open chromatin architecture), as well enhancer looping gene promoters. In absence eRNA production, strong these not observed, even though ESR1 evident. find flavopiridol, CDK9 inhibitor blocks elongation, inhibits but does affect other molecular indicators activity, suggesting occurs after assembly active enhancers. Finally, show “signature” based on GRO-seq can be used for de novo prediction across cell types. Together, our studies shed new light activity its insights about function.