Systematic dissection of transcriptional regulatory networks by genome-scale and single-cell CRISPR screens
Kathleen Sprouffske, Rui Lopes, Caibin Sheng, Esther C. H. Uijttewaal, Adriana Emma Wesdorp, Jan Dahinden, Simon Wengert, Juan Diaz-Miyar, Umut Yildiz, Melusine Bleu, Verena Apfel, Fanny Mermet-Meillon, Rok Krese, Mathias Eder, André Vidas Olsen, Philipp Hoppe, Judith Knehr, Walter Carbone, Rachel Cuttat, Annick Waldt, Marc Altorfer, Ulrike Naumann, Joachim Weischenfeldt, Antoine DeWeck, Audrey Kauffmann … & Giorgio G. Galli
Millions of putative transcriptional regulatory elements (TREs) have been cataloged in the human genome, yet their functional relevance in specific pathophysiological settings remains to be determined. This is critical to understand how oncogenic transcription factors (TFs) engage specific TREs to impose transcriptional programs underlying malignant phenotypes. Here, we combine cutting edge CRISPR screens and epigenomic profiling to functionally survey ≈15,000 TREs engaged by estrogen receptor (ER). We show that ER exerts its oncogenic role in...