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调控DNA的功能足迹分析

Functional footprinting of regulatory DNA.

作者信息

Vierstra Jeff, Reik Andreas, Chang Kai-Hsin, Stehling-Sun Sandra, Zhou Yuanyue, Hinkley Sarah J, Paschon David E, Zhang Lei, Psatha Nikoletta, Bendana Yuri R, O'Neil Colleen M, Song Alexander H, Mich Andrea K, Liu Pei-Qi, Lee Gary, Bauer Daniel E, Holmes Michael C, Orkin Stuart H, Papayannopoulou Thalia, Stamatoyannopoulos George, Rebar Edward J, Gregory Philip D, Urnov Fyodor D, Stamatoyannopoulos John A

机构信息

Department of Genome Sciences, University of Washington, Seattle, Washington, USA.

Sangamo BioSciences, Pt. Richmond, California, USA.

出版信息

Nat Methods. 2015 Oct;12(10):927-30. doi: 10.1038/nmeth.3554. Epub 2015 Aug 31.

Abstract

Regulatory regions harbor multiple transcription factor (TF) recognition sites; however, the contribution of individual sites to regulatory function remains challenging to define. We describe an approach that exploits the error-prone nature of genome editing-induced double-strand break repair to map functional elements within regulatory DNA at nucleotide resolution. We demonstrate the approach on a human erythroid enhancer, revealing single TF recognition sites that gate the majority of downstream regulatory function.

摘要

调控区域含有多个转录因子(TF)识别位点;然而,单个位点对调控功能的贡献仍难以确定。我们描述了一种利用基因组编辑诱导的双链断裂修复的易错性质,以核苷酸分辨率绘制调控DNA内功能元件图谱的方法。我们在人类红系增强子上展示了该方法,揭示了控制大部分下游调控功能的单个TF识别位点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f69/5381659/301d793c5356/nihms713696f1.jpg

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