CRISPR-Mediated Synergistic Epigenetic and Transcriptional Control.

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    • Source:
      Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 101738191 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2573-1602 (Electronic) Linking ISSN: 25731599 NLM ISO Abbreviation: CRISPR J Subsets: MEDLINE
    • Publication Information:
      Original Publication: [New Rochelle, NY] : Mary Ann Liebert, Inc., [2018]-
    • Subject Terms:
    • Abstract:
      Targeted activation of endogenous genes is an important approach for cell engineering. Here, we report that the nuclease-deactivated dCas9 fused to a transcriptional activator (VPR) and an epigenetic effector (the catalytic domain of histone acetyltransferase p300 core ) simultaneously, sequentially, or as a single quadripartite effector can lead to enhanced activation of target genes. The composite activator, VPRP, behaves more efficiently than individual activators across a set of genes in different cell types. We characterize off-target effects for host chromatin acetylation and transcriptome using the effectors. Our work demonstrates that transcriptional and epigenetic effectors can be used together to enhance gene activation and suggests the need for further optimization of epigenetic effectors to reduce off-targets.
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    • Grant Information:
      U01 DK127405 United States DK NIDDK NIH HHS
    • Publication Date:
      Date Created: 20220310 Date Completed: 20220421 Latest Revision: 20230506
    • Publication Date:
      20240104
    • Accession Number:
      PMC9206482
    • Accession Number:
      10.1089/crispr.2021.0099
    • Accession Number:
      35271371