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Abstract

The growth of human cancer cells is driven by aberrant enhancer and gene transcription activity. Here, we use transient transcriptome sequencing (TT‐seq) to map thousands of transcriptionally active putative enhancers in fourteen human cancer cell lines covering seven types of cancer. These enhancers were associated with cell type‐specific gene expression, enriched for genetic variants that predispose to cancer, and included functionally verified enhancers. Enhancer–promoter (E–P) pairing by correlation of transcription activity revealed ~ 40,000 putative E–P pairs, which were depleted for housekeeping genes and enriched for transcription factors, cancer‐associated genes, and 3D conformational proximity. The cell type specificity and transcription activity of target genes increased with the number of paired putative enhancers. Our results represent a rich resource for future studies of gene regulation by enhancers and their role in driving cancerous cell growth.