Transcriptionally active enhancers in human cancer cells

• Published in: Molecular systems biology 2021-01, Vol.17 (1), p.e9873-n/a
• Main Authors: Lidschreiber, Katja, Jung, Lisa A, von der Emde, Henrik, Dave, Kashyap, Taipale, Jussi, Cramer, Patrick, Lidschreiber, Michael
• Format: Article
• Language: English
• Subjects: Binding sites; Cancer; Cell Line, Tumor; Deoxyribonucleic acid; DNA; EMBO03; EMBO09; Enhancer Elements, Genetic; Enhancers; eRNAs; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Gene regulation; Gene Regulatory Networks; Genes; Genetic diversity; Genetic variance; Genomes; Genomics; HCT116 Cells; Humans; Leukemia; Medicin och hälsovetenskap; Mutation; Neoplasms - genetics; Organ Specificity; Prostate; RNA polymerase; Sequence Analysis, DNA - methods; Sequence Analysis, RNA; transcription; Transcription factors; Transcriptional Activation; Transcriptomes; TT‐seq; Tumor cell lines; Uterine cancer
• ISSN: 1744-4292; 1744-4292
• DOI: 10.15252/msb.20209873

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. SYNOPSIS TT‐seq measures genome‐wide enhancer transcription with high sensitivity in human cancer cells. The resulting comprehensive annotation of putative enhancers and enhancer‐promoter pairs serves as a valuable resource for studying enhancer function. TT‐seq maps thousands of transcriptionally active, putative enhancers in fourteen human cancer cell lines covering seven types of cancer. Enhancer‐promoter (E–P) pairing by correlation of transcription activity reveals ~ 40,000 putative E–P pairs. A catalog comprising candidate enhancers with cancer‐associated somatic mutations and putative E–P pairs involving cancer‐associated genes is generated. This resource serves as a valuable tool to study gene regulation by enhancers. Graphical Abstract TT‐seq measures genome‐wide enhancer transcription with high sensitivity in human cancer cells. The resulting comprehensive annotation of putative enhancers and enhancer‐promoter pairs serves as a valuable resource for studying enhancer function.