Broad genic repression domains signify enhanced silencing of oncogenes
| Autor: | Min Zhang, Alin Tomoiaga, Jie Lv, Lili Zhang, Kaifu Chen, Qingshu Meng, Bo Xia, Dongyu Zhao, Sen Zhu, Qi Cao, Guangyu Wang, John P. Cooke, Xinlei Gao, Yang Yi, Min Gyu Lee |
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| Rok vydání: | 2020 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine Transcription Elongation Genetic Science General Physics and Astronomy Breast Neoplasms Regulatory Sequences Nucleic Acid Methylation Article General Biochemistry Genetics and Molecular Biology Histones 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Humans Gene silencing Epigenetics Nucleotide Motifs lcsh:Science Gene Psychological repression Conserved Sequence Transcription Initiation Genetic Cell Proliferation Epigenomics Genetics Regulation of gene expression Multidisciplinary biology Lysine food and beverages Oncogenes General Chemistry Chromatin Gene Expression Regulation Neoplastic 030104 developmental biology Histone 030220 oncology & carcinogenesis biology.protein lcsh:Q Female RNA Long Noncoding |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Epigenetically altered genes can have a key role in cancer pathobiology but epigenetic signatures that distinguish oncogenes are not yet known. Here, the authors identify broad genic repression domains, defined by widespread H3K27me3 modification, as an epigenetic signature to provide mutation-independent information for discovery of potential oncogenes. |
| Databáze: | OpenAIRE |
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