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DOI | 10.1038/s41467-018-08017-9 |
Rapid and reversible epigenome editing by endogenous chromatin regulators | |
Braun, Simon M. G.1,2; Kirkland, Jacob G.1,2; Chory, Emma J.1,2,3; Husmann, Dylan1,2; Calarco, Joseph P.1,2; Crabtree, Gerald R.1,2,4 | |
2019-01-10 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000410812200007 |
WOS关键词 | TRANSCRIPTIONAL ACTIVATION ; GENE-EXPRESSION ; HISTONE H3 ; STEM-CELLS ; LYSINE 9 ; GENOME ; COMPLEX ; HETEROCHROMATIN ; PLURIPOTENT ; MODULATION |
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/204154 |
专题 | 资源环境科学 |
作者单位 | 1.Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA; 2.Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA; 3.Stanford Univ, Dept Chem Engn, Stanford, CA 94305 USA; 4.Howard Hughes Med Inst, Chevy Chase, MD 20815 USA |
推荐引用方式 GB/T 7714 | Braun, Simon M. G.,Kirkland, Jacob G.,Chory, Emma J.,et al. Rapid and reversible epigenome editing by endogenous chromatin regulators[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Braun, Simon M. G.,Kirkland, Jacob G.,Chory, Emma J.,Husmann, Dylan,Calarco, Joseph P.,&Crabtree, Gerald R..(2019).Rapid and reversible epigenome editing by endogenous chromatin regulators.NATURE COMMUNICATIONS,8. |
MLA | Braun, Simon M. G.,et al."Rapid and reversible epigenome editing by endogenous chromatin regulators".NATURE COMMUNICATIONS 8(2019). |
条目包含的文件 | 条目无相关文件。 |
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