Broad genic repression domains signify enhanced silencing of oncogenes
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 03, 2020
- Source ID
- 10.1038/s41467-020-18913-8
Entities
People
- Alin S. Tomoiaga
- Bo Xia
- Dongyu Zhao
- Guangyu Wang
- Jie Lv
- John P. Cooke
- Kaifu Chen
- Lili Zhang
- Min Gyu Lee
- Min Zhang
- Qi Cao
- Qingshu Meng
- Sen Zhu
- Xinlei Gao
- Yang Yi
Organizations
- American Cancer Society
- Foundation for the National Institutes of Health
- Prostate Cancer Foundation
- United States Department of Defense