CRISPR/Cas9-Based Engineering of the Epigenome

Pulecio, Julián; Verma, Nipun; Mejía-Ramírez, Eva; Huangfu, Danwei; Raya, Ángel

doi:10.1016/j.stem.2017.09.006

Cited by 231 publications

(150 citation statements)

References 194 publications

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“…Which molecules are involved in the initiation and progression of cancer genotypes with expanding CSCs of each tumor type [164]? CRISPR-mediated epigenome editing may be a promising technique to identify the key cis -elements in the genomes of CSCs [165–168]. The origins of cancer stemness and the manners in which stemness genes and oncogenes might be separated remain unclear.…”

Section: Obstacles To Cancer Cell Reprogrammingmentioning

confidence: 99%

Potential application of cell reprogramming techniques for cancer research

Saito

Lin

Nakamura

et al. 2018

Cell. Mol. Life Sci.

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The ability to control the transition from an undifferentiated stem cell to a specific cell fate is one of the key techniques that are required for the application of interventional technologies to regenerative medicine and the treatment of tumors and metastases and of neurodegenerative diseases. Reprogramming technologies, which include somatic cell nuclear transfer, induced pluripotent stem cells, and the direct reprogramming of specific cell lineages, have the potential to alter cell plasticity in translational medicine for cancer treatment. The characterization of cancer stem cells (CSCs), the identification of oncogene and tumor suppressor genes for CSCs, and the epigenetic study of CSCs and their microenvironments are important topics. This review summarizes the application of cell reprogramming technologies to cancer modeling and treatment and discusses possible obstacles, such as genetic and epigenetic alterations in cancer cells, as well as the strategies that can be used to overcome these obstacles to cancer research.

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Section: Obstacles To Cancer Cell Reprogrammingmentioning

confidence: 99%

Potential application of cell reprogramming techniques for cancer research

Saito

Lin

Nakamura

et al. 2018

Cell. Mol. Life Sci.

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“…Advances in artificial transcription factor (ATF) technologies have enabled direct control of gene expression and epigenetic states 18,19,20 . CRISPR/Cas9-based technologies allow much flexibility and scalability because the specificity is programmable by a single guide RNA (sgRNA) 21,22 .…”

Section: Introductionmentioning

confidence: 99%

Casilio-ME: Enhanced CRISPR-based DNA demethylation by RNA-guided coupling methylcytosine oxidation and DNA repair pathways

Taghbalout

Jillette

et al. 2019

Preprint

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We have developed a methylation editing toolbox, Casilio-ME, that enables not only RNA-guided methylcytosine editing by targeting TET1 to genomic sites, but also by codelivering TET1 and protein factors that couple methylcytosine oxidation to DNA repair activities, and/or promote TET1 to achieve enhanced activation of methylation-silenced genes. Delivery of TET1 activity by Casilio-ME1 robustly altered the CpG methylation landscape of promoter regions and activated methylation-silenced genes. We augmented Casilio-ME1 to simultaneously deliver the TET1-catalytic domain and GADD45A (Casilio-ME2) or NEIL2 (Casilio-ME3) to streamline removal of oxidized cytosine intermediates to enhance activation of targeted genes. Using two-in-one effectors or modular effectors, Casilio-ME2 and Casilio-ME3 remarkably boosted gene activation and methylcytosine demethylation of targeted loci. We expanded the toolbox to enable a stable and expression-inducible system for broader application of the Casilio-ME platforms. This work establishes an advanced platform for editing DNA methylation to enable transformative research investigations interrogating DNA methylomes.

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“…By mutating the catalytic sites of the Cas9 endonuclease, a catalytically inactive or "dead" Cas9 (dCas9) has been developed (5). Various dCas9 fusion proteins have subsequently been designed, and the dCas9 system can be used for a variety of new applications, including the activation or repression of gene transcription, site-specific chromatin modification, or visualization of specific chromosome sites in living cells -see (6,7) for reviews.…”

Section: Introductionmentioning

confidence: 99%

A method for rapid selection of randomly induced mutations in a gene of interest using CRISPR/Cas9 mediated activation of gene expression

Chen

et al. 2019

Preprint

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Running title: Rapid selection of randomly induced mutations using CRISPR/Cas9 AbstractWe have developed a CRISPR/Cas9 based method for isolating randomly induced recessive lethal mutations in a gene of interest (GOI) by phenotype selection within the F1 progeny of a single genetic cross. Our method takes advantage of the ability to overexpress a GOI using CRISPR/Cas9 mediated activation of gene expression. In essence, the screening strategy is based upon the idea that if overexpression of a wild type allele can generate a phenotype, then overexpression of a newly induced loss-offunction allele will lack this phenotype. This method also depends on the use of CRISPR/Cas9 based mutagenesis to recover alleles of a GOI that are refractory to CRISPR/Cas9 mediated activation of gene expression but are otherwise wild type. As a proof-of-principle, we used this method to select EMS induced mutations of the Drosophila gene hindsight (hnt). From approximately 45,000 F1 progeny we recovered 8 new EMS induced loss-of-function hnt alleles. This new method can, in theory, be applied to any circumstance where CRISPR/Cas9 mediated activation of gene expression is associated with lethality or a visible phenotype.

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CRISPR/Cas9-Based Engineering of the Epigenome

Cited by 231 publications

References 194 publications

Potential application of cell reprogramming techniques for cancer research

Potential application of cell reprogramming techniques for cancer research

Casilio-ME: Enhanced CRISPR-based DNA demethylation by RNA-guided coupling methylcytosine oxidation and DNA repair pathways

A method for rapid selection of randomly induced mutations in a gene of interest using CRISPR/Cas9 mediated activation of gene expression

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