Transcriptional dysregulation by aberrant enhancer activation and rewiring in cancer.
Transcriptional dysregulation by aberrant enhancer activation and rewiring in cancer.
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DOI：
10.1111/cas.14884
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发表时间：
2021-06
期刊：
影响因子：
5.7
通讯作者：
Kaneda A
中科院分区：
文献类型：
--
作者：
Okabe A;Kaneda A
细胞的同一性是由基因组内的调控元件控制的，如启动子、增强子和绝缘子。这些调控元件在细胞核中相互作用并形成组织特异性染色质结构。这些元素及其相互作用的失调可导致细胞身份的丧失并促进疾病如癌症的发展。肿瘤细胞通过各种机制在致癌驱动基因处获得异常激活的增强子。小的基因组变化如突变、插入和扩增可形成异常增强子。染色体水平的基因组重排，包括易位和倒位，也经常在癌症中观察到。这些重排可以导致增强子重新定位到肿瘤类型特异性癌基因附近的位置。由基因组或表观基因组变化引起的染色质结构变化导致增强子和原癌基因之间的错误相互作用，最终通过激活致癌信号促进肿瘤发生。另外的表观基因组机制也可以引起异常的增强子激活，包括与致癌转录因子的过表达和转录辅因子的突变相关的那些。外源性病毒DNA也可导致增强子畸变。在这里，我们回顾了通过增强子激活和重新连接引起的异常癌基因激活的机制，这两者都是由非编码区的基因组或表观基因组改变引起的。由基因组变化引起的染色质结构变化，包括突变、插入、扩增或染色体易位和倒位，导致增强子和原癌基因之间的错误相互作用，最终通过激活致癌信号促进肿瘤发生。表观基因组机制也可以引起异常的增强子激活，包括与致癌转录因子的过表达和转录辅因子的突变相关的那些。在这里，我们通过异常的增强子激活和重新布线来综述这些致瘤机制，这应该有助于理解非编码区的基因组或表观基因组改变如何有助于癌症的发展。
Cell identity is controlled by regulatory elements, such as promoters, enhancers, and insulators, within the genome. These regulatory elements interact in the nucleus and form tissue‐specific chromatin structures. Dysregulation of these elements and their interactions can lead to loss of cell identity and promote the development of diseases such as cancer. Tumor cells acquire aberrantly activated enhancers at oncogenic driver genes through various mechanisms. Small genomic changes such as mutations, insertions, and amplifications can form aberrant enhancers. Genomic rearrangements at the chromosomal level, including translocations and inversions, are also often observed in cancers. These rearrangements can result in repositioning of enhancers to locations near tumor‐type‐specific oncogenes. Chromatin structural changes caused by genomic or epigenomic changes lead to mis‐interaction between enhancers and proto‐oncogenes, ultimately contributing to tumorigenesis through activation of oncogenic signals. Additional epigenomic mechanisms can also cause aberrant enhancer activation, including those associated with overexpression of oncogenic transcription factors and the mutation of transcriptional cofactors. Exogenous viral DNA can also lead to enhancer aberrations. Here, we review the mechanisms underlying aberrant oncogene activation through enhancer activation and rewiring, both of which are caused by genomic or epigenomic alterations in non‐coding regions. Chromatin structural changes caused by genomic changes, including mutations, insertions, amplifications, or chromosomal translocations and inversions, lead to mis‐interaction between enhancers and proto‐oncogenes, ultimately contributing to tumorigenesis through activation of oncogenic signals. Epigenomic mechanisms can also cause aberrant enhancer activation, including those associated with overexpression of oncogenic transcription factors and the mutation of transcriptional cofactors. Here, we review these tumorigenic mechanisms through aberrant enhancer activation and rewiring that should help to understand how genomic or epigenomic alterations in non‐coding regions can contribute to cancer development.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Groeschel, Stefan;Sanders, Mathijs A.;Delwel, Ruud
通讯作者：
Delwel, Ruud
影响因子：
16.6
作者：
Helmsauer K;Valieva ME;Ali S;Chamorro González R;Schöpflin R;Röefzaad C;Bei Y;Dorado Garcia H;Rodriguez-Fos E;Puiggròs M;Kasack K;Haase K;Keskeny C;Chen CY;Kuschel LP;Euskirchen P;Heinrich V;Robson MI;Rosswog C;Toedling J;Szymansky A;Hertwig F;Fischer M;Torrents D;Eggert A;Schulte JH;Mundlos S;Henssen AG;Koche RP
通讯作者：
Koche RP