Systematic discovery and functional dissection of enhancers needed for cancer cell fitness and proliferation

• DOI: 10.1016/j.celrep.2022.111630
• Publication Date: 2022-11-08T11:07:02Z
• Authors: Poshen B. Chen; Patrick C. Fiaux; Kai Zhang; Bin Li; Naoki Kubo; Shan Jiang; Rong Hu; Emma Rooholfada; Sihan Wu; Mengchi Wang; Wei Wang; Graham McVicker; Paul S. Mischel; Bing Ren
• Keywords: Enhancer RNAs

A scarcity of functionally validated enhancers in the human genome presents a significant hurdle to understanding how these cis-regulatory elements contribute diseases. We carry out highly multiplexed CRISPR-based perturbation and sequencing identify required for cell proliferation fitness 10 cancer lines. Our results suggest that enhancers, unlike their target genes, display high cell-type specificity chromatin features. They typically adopt modular structure, comprised activating enriched motifs oncogenic transcription factors, surrounded by repressive recognized factors with tumor suppressor functions. further are selectively accessible clinical samples, levels accessibility associated patient survival. These reveal functional across multiple lines, characterize context-dependent organization, yield insights into altered programs cells.