Chemically Controlled Epigenome Editing through an Inducible dCas9 System

Chen, Tingjun; Gao, Dan; Zhang, Roushu; Zeng, Guihua; Hao, Yan; Lim, Eunju; Liang, Fu‐Sen

doi:10.1021/jacs.7b06555

Cited by 63 publications

(47 citation statements)

References 29 publications

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“…The CiA system described above utilized a knock-in DNA sequence at the OCT4 locus to enable the recruitment of epigenome modifiers through corresponding DBDs, which limits the inducible epigenome editing or remodeling to occur only at this particular locus. To offer a more versatile temporal-controlled epigenome editing platform, CRISPR/dCas9 was combined with the ABA-based CIP method to temporally target the ABI-fused p300 HAT core domain via PYL-fused dCas9 to the promoter region of IL1RN, MYOD1, GRM2 and HBA genes in human HEK293T cells leading to increased H3K27ac and gene activation (Figure 2b) [86]. With the fast dimerization kinetics that ABA CIP offers, the p300 HAT recruitment, H3K27ac installation and mRNA expression can be monitored following its precise time course, allowing the establishment of their causal relationship [86].…”

Section: Chemically Induced Proximity (Cip)-based Editingmentioning

confidence: 99%

“…To offer a more versatile temporal-controlled epigenome editing platform, CRISPR/dCas9 was combined with the ABA-based CIP method to temporally target the ABI-fused p300 HAT core domain via PYL-fused dCas9 to the promoter region of IL1RN, MYOD1, GRM2 and HBA genes in human HEK293T cells leading to increased H3K27ac and gene activation (Figure 2b) [86]. With the fast dimerization kinetics that ABA CIP offers, the p300 HAT recruitment, H3K27ac installation and mRNA expression can be monitored following its precise time course, allowing the establishment of their causal relationship [86]. Furthermore, the reversibility of the ABA CIP system allowed the rapid removal of inducer and the dislodge of P300 HAT from the targeted locus, offering an opportunity to assess the stability of artificially installed H3K27ac and a model to study epigenetic memory [87,88].…”

Section: Chemically Induced Proximity (Cip)-based Editingmentioning

confidence: 99%

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Chemical and Light Inducible Epigenome Editing

Zhao

Wang

Liang

2020

IJMS

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The epigenome defines the unique gene expression patterns and resulting cellular behaviors in different cell types. Epigenome dysregulation has been directly linked to various human diseases. Epigenome editing enabling genome locus-specific targeting of epigenome modifiers to directly alter specific local epigenome modifications offers a revolutionary tool for mechanistic studies in epigenome regulation as well as the development of novel epigenome therapies. Inducible and reversible epigenome editing provides unique temporal control critical for understanding the dynamics and kinetics of epigenome regulation. This review summarizes the progress in the development of spatiotemporal-specific tools using small molecules or light as inducers to achieve the conditional control of epigenome editing and their applications in epigenetic research.

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Section: Chemically Induced Proximity (Cip)-based Editingmentioning

confidence: 99%

Section: Chemically Induced Proximity (Cip)-based Editingmentioning

confidence: 99%

Chemical and Light Inducible Epigenome Editing

Zhao

Wang

Liang

2020

IJMS

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“…For example, the CRISPR–Cas system allows programmable control at multiple gene targets, using a catalytically inactive Cas9 (dCas9), a single guide RNA (sgRNA) to target DNA, and an associated effector protein to regulate transcription . Furthermore, chemically inducible systems that control the assembly, stability, or activity of the CRISPR–Cas complex can be used to regulate the timing of gene expression …”

Section: Figurementioning

confidence: 99%

CRISPR–Cas‐Mediated Chemical Control of Transcriptional Dynamics in Yeast

et al. 2019

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Synthetic CRISPR–Cas transcription factors enable the construction of complex gene‐expression programs, and chemically inducible systems allow precise control over the expression dynamics. To provide additional modes of regulatory control, we have constructed a chemically inducible CRISPR activation (CRISPRa) system in yeast that is mediated by recruitment to MS2‐functionalized guide RNAs. We use reporter gene assays to systematically map the dose dependence, time dependence, and reversibility of the system. Because the recruitment function is encoded at the level of the guide RNA, it is straightforward to target multiple genes and independently regulate expression dynamics at individual targets. This approach provides a new method to engineer sophisticated, multigene programs with precise control over the dynamics of gene expression.

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“…This base‐editing method will have tremendous advantages because DNA cleavage can result in cytotoxicity. Besides, controlled activation of enzymes for genome or epigenome editing by stimulation with small organic molecules or irradiation by light have shown that enzymes can be switched on/off at will . Further understanding of epigenetic mechanisms is required for specific epigenome regulation; the study of relationships between modification of histone proteins and DNA modification .…”

Section: Other Genome Editing Technologies and Future Directionsmentioning

confidence: 99%

Development of Toolboxes for Precision Genome/Epigenome Editing and Imaging of Epigenetics

Nomura

2018

The Chemical Record

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Zinc finger (ZF) proteins are composed of repeated ββα modules and coordinate a zinc ion. ZF domains recognizing specific DNA target sequences can be substituted for the binding domains of various DNA-modifying enzymes to create designer nucleases, recombinases, and methyltransferases with programmable sequence specificity. Enzymatic genome editing and modification can be applied to many fields of basic research and medicine. The recent development of new platforms using transcription activator-like effector (TALE) proteins or the CRISPR-Cas9 system has expanded the range of possibilities for genome-editing technologies. In addition, these DNA binding domains can also be utilized to build a toolbox for epigenetic controls by fusing them with protein- or DNA-modifying enzymes. Here, our research on epigenome editing including the development of artificial zinc finger recombinase (ZFR), split DNA methyltransferase, and fluorescence imaging of histone proteins by ZIP tag-probe system is introduced. Advances in the ZF, TALE, and CRISPR-Cas9 platforms have paved the way for the next generation of genome/epigenome engineering approaches.

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Chemically Controlled Epigenome Editing through an Inducible dCas9 System

Cited by 63 publications

References 29 publications

Chemical and Light Inducible Epigenome Editing

Chemical and Light Inducible Epigenome Editing

CRISPR–Cas‐Mediated Chemical Control of Transcriptional Dynamics in Yeast

Development of Toolboxes for Precision Genome/Epigenome Editing and Imaging of Epigenetics

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