Broad genic repression domains signify enhanced silencing of oncogenes
NATURE COMMUNICATIONS
Authors: Zhao, Dongyu; Zhang, Lili; Zhang, Min; Xia, Bo; Lv, Jie; Gao, Xinlei; Wang, Guangyu; Meng, Qingshu; Yi, Yang; Zhu, Sen; Tomoiaga, Alin S.; Lee, Min Gyu; Cooke, John P.; Cao, Qi; Chen, Kaifu
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. 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.
Nucleosomes and Epigenetics from a Chemical Perspective
CHEMBIOCHEM
Authors: Feng, Yihong; Endo, Masayuki; Sugiyama, Hiroshi
Abstract
Nucleosomes, which are the fundamental building blocks of chromatin, are highly dynamic, they play vital roles in the formation of higher-order chromatin structures and orchestrate gene regulation. Nucleosome structures, histone modifications, nucleosome-binding proteins, and their functions are being gradually unravelled with the development of epigenetics. With the continuous development of research approaches such as cryo-EM, FRET and next-generation sequencing for genome-wide analysis of nucleosomes, the understanding of nucleosomes is getting wider and deeper. Herein, we review recent progress in research on nucleosomes and epigenetics, from nucleosome structure to chromatin formation, with a focus on chemical aspects. Basic knowledge of the nucleosome (nucleosome structure, nucleosome position sequence, nucleosome assembly and remodeling), epigenetic modifications, chromatin structure, chemical biology methods and nucleosome, observation nucleosome by AFM, phase separation and nucleosomes are described in this review.