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DOI | 10.1126/science.aan6414 |
Synthetic transcription elongation factors license transcription across repressive chromatin | |
Erwin, Graham S.1; Grieshop, Matthew P.1; Ali, Asfa1; Qi, Jun2; Lawlor, Matthew2; Kumar, Deepak3,4; Ahmad, Istaq3,4; McNally, Anna5; Teider, Natalia5; Worringer, Katie5; Sivasankaran, Rajeev5; Syed, Deeba N.6; Eguchi, Asuka1; Ashraf, Md.1; Jeffery, Justin7; Xu, Mousheng2; Park, Paul M. C.2; Mukhtar, Hasan6; Srivastava, Achal K.3; Faruq, Mohammed4; Bradner, James E.2,5; Ansari, Aseem Z.1,8 | |
2017-12-22 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 358期号:6370页码:1617-1621 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; India |
英文摘要 | The release of paused RNA polymerase II into productive elongation is highly regulated, especially at genes that affect human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that engages the transcription elongation machinery. By limiting activity to targeted loci, Syn-TEFs convert constituent modules from broad-spectrum inhibitors of transcription into gene-specific stimulators. Here we present Syn-TEF1, a molecule that actively enables transcription across repressive GAA repeats that silence frataxin expression in Friedreich's ataxia, a terminal neurodegenerative disease with no effective therapy. The modular design of Syn-TEF1 defines a general framework for developing a class of molecules that license transcription elongation at targeted genomic loci. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000418448000066 |
WOS关键词 | FRIEDREICH ATAXIA ; CELL FATE ; GENE ; DNA ; REPEATS ; INHIBITION ; MOLECULES ; COMPLEX |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197613 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Wisconsin Madison, Dept Biochem, Madison, WI 53706 USA; 2.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA; 3.All India Inst Med Sci, Dept Neurol, New Delhi, India; 4.CSIR, IGIB, Genom & Mol Med, New Delhi, India; 5.NIBR, Cambridge, MA 02139 USA; 6.Univ Wisconsin Madison, Dept Dermatol, Madison, WI 53706 USA; 7.Univ Wisconsin, Carbone Canc Ctr, Small Anim Imaging Facil, Madison, WI 53792 USA; 8.Univ Wisconsin Madison, Genome Ctr Wisconsin, Madison, WI 53706 USA |
推荐引用方式 GB/T 7714 | Erwin, Graham S.,Grieshop, Matthew P.,Ali, Asfa,et al. Synthetic transcription elongation factors license transcription across repressive chromatin[J]. SCIENCE,2017,358(6370):1617-1621. |
APA | Erwin, Graham S..,Grieshop, Matthew P..,Ali, Asfa.,Qi, Jun.,Lawlor, Matthew.,...&Ansari, Aseem Z..(2017).Synthetic transcription elongation factors license transcription across repressive chromatin.SCIENCE,358(6370),1617-1621. |
MLA | Erwin, Graham S.,et al."Synthetic transcription elongation factors license transcription across repressive chromatin".SCIENCE 358.6370(2017):1617-1621. |
条目包含的文件 | 条目无相关文件。 |
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