Transcriptionally active enhancers in human cancer cells

Mol Syst Biol. 2021 Jan;17(1):e9873. doi: 10.15252/msb.20209873.

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.

Keywords: TT-seq; cancer; eRNAs; enhancers; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Enhancer Elements, Genetic*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • HCT116 Cells
  • Humans
  • Mutation
  • Neoplasms / genetics*
  • Organ Specificity
  • Sequence Analysis, DNA / methods*
  • Sequence Analysis, RNA
  • Transcriptional Activation

Associated data

  • GEO/GSE152291