Broad genic repression domains signify enhanced silencing of oncogenes

Dongyu Zhao, Lili Zhang, Min Zhang, Bo Xia, Jie Lv, Xinlei Gao, Guangyu Wang, Qingshu Meng, Yang Yi, Sen Zhu, Alin S. Tomoiaga, Min Gyu Lee, John P. Cooke, Qi Cao, Kaifu Chen

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Cancers result from a set of genetic and epigenetic alterations. Most known oncogenes were identified by gain-of-function mutations in cancer, yet little is known about their epigenetic features. Through integrative analysis of 11,596 epigenomic profiles and mutations from >8200 tumor-normal pairs, we discover broad genic repression domains (BGRD) on chromatin as an epigenetic signature for oncogenes. A BGRD is a widespread enrichment domain of the repressive histone modification H3K27me3 and is further enriched with multiple other repressive marks including H3K9me3, H3K9me2, and H3K27me2. Further, BGRD displays widespread enrichment of repressed cis-regulatory elements. Shortening of BGRDs is linked to derepression of transcription. BGRDs at oncogenes tend to be conserved across normal cell types. Putative tumor-promoting genes and lncRNAs defined using BGRDs are experimentally verified as required for cancer phenotypes. Therefore, BGRDs play key roles in epigenetic regulation of cancer and provide a direction for mutation-independent discovery of oncogenes.

Original languageEnglish (US)
Article number5560
Pages (from-to)5560
JournalNature Communications
Issue number1
StatePublished - Nov 3 2020


  • Breast Neoplasms/genetics
  • CD4-Positive T-Lymphocytes/metabolism
  • Cell Line, Tumor
  • Cell Movement/genetics
  • Cell Proliferation/genetics
  • Chromatin/genetics
  • Conserved Sequence/genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Histones/metabolism
  • Humans
  • Lysine/metabolism
  • Methylation
  • Nucleotide Motifs/genetics
  • Oncogenes
  • RNA, Long Noncoding/genetics
  • Regulatory Sequences, Nucleic Acid/genetics
  • Transcription Elongation, Genetic
  • Transcription Initiation, Genetic

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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