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Combining compact human protein domains with CRISPR systems for robust gene activation

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Here we developed synthetic transactivation domains (TADs) built from human mechanosensitive transcription factors (MTFs). By linking MTF TAD segments together, we engineered compact and potent multipartite transcriptional activation modules. We then harnessed these modules to create a CRISPR activation system, which we termed the dCas9 recruited enhanced activation module (CRISPR-DREAM).

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Fig. 1: Potent gene activation using CRISPR-DREAM and an all-in-one AAV CRISPRa tool.

References

  1. Gilbert, L. A. et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154, 442–451 (2013). This article was one of the first studies to demonstrate CRISPR-mediated transcriptional regulation in human cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wang, K. et al. Systematic comparison of CRISPR-based transcriptional activators uncovers gene-regulatory features of enhancer-promoter interactions. Nucleic Acids Res. 50, 7842–7855 (2022). This article compared the expression levels and relative efficacies of different state-of-the-art CRISPRa tools in human cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Weuring, W. J. et al. CRISPRa-mediated upregulation of scn1laa during early development causes epileptiform activity and dCas9-associated toxicity. CRISPR J. 4, 575–582 (2021). This article demonstrates that some CRISPRa tools can be toxic in some contexts.

    Article  PubMed  Google Scholar 

  4. Konermann, S. et al. Genome-scale transcriptional activation by an engineered CRISPR–Cas9 complex. Nature 517, 583–588 (2015). In this article, the authors developed the potent and widely used SAM CRISPRa tool.

    Article  CAS  PubMed  Google Scholar 

  5. Chavez, A. et al. Highly efficient Cas9-mediated transcriptional programming. Nat. Methods 12, 326–328 (2015). In this article, the authors developed the potent and widely used dCas9–VPR tool.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This is a summary of: Mahata, B. et al. Compact engineered human mechanosensitive transactivation modules enable potent and versatile synthetic transcriptional control. Nat. Methods https://doi.org/10.1038/s41592-023-02036-1 (2023).

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Combining compact human protein domains with CRISPR systems for robust gene activation. Nat Methods 20, 1635–1636 (2023). https://doi.org/10.1038/s41592-023-02038-z

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  • DOI: https://doi.org/10.1038/s41592-023-02038-z

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