https://scholars.lib.ntu.edu.tw/handle/123456789/626757
標題: | TERRA regulates DNA G-quadruplex formation and ATRX recruitment to chromatin | 作者: | Tsai, Ru-Xuan Fang, Kuo-Chen Yang, Po-Cheng Hsieh, Yu-Hung Chiang, I-Tien Chen, Yunfei Lee, Hun-Goo Lee, Jeannie T HSUEH-PING CHU |
關鍵字: | REPEAT-CONTAINING RNA; FORMING SEQUENCES; R-LOOPS; PROMOTER; EXPRESSION; REVEALS; BINDING; LOCI | 公開日期: | 28-十一月-2022 | 出版社: | OXFORD UNIV PRESS | 卷: | 50 | 期: | 21 | 來源出版物: | Nucleic acids research | 摘要: | The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and differentially expressed genes. Loss of ATRX alleviates the effect of gene repression caused by TERRA depletion. Immunostaining analyses demonstrate that knockdown of TERRA diminishes DNA G4 signals, whereas silencing ATRX elevates G4 formation. Our results uncover an epigenetic regulation by TERRA that sequesters ATRX and preserves DNA G4 structures. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/626757 | ISSN: | 0305-1048 | DOI: | 10.1093/nar/gkac1114 |
顯示於: | 分子與細胞生物學研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。