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Nanobody-mediated control of gene expression and epigenetic memory

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  • Mike V. Van

    (Stanford University)

  • Taihei Fujimori

    (Stanford University)

  • Lacramioara Bintu

    (Stanford University)

Abstract

Targeting chromatin regulators to specific genomic locations for gene control is emerging as a powerful method in basic research and synthetic biology. However, many chromatin regulators are large, making them difficult to deliver and combine in mammalian cells. Here, we develop a strategy for gene control using small nanobodies that bind and recruit endogenous chromatin regulators to a gene. We show that an antiGFP nanobody can be used to simultaneously visualize GFP-tagged chromatin regulators and control gene expression, and that nanobodies against HP1 and DNMT1 can silence a reporter gene. Moreover, combining nanobodies together or with other regulators, such as DNMT3A or KRAB, can enhance silencing speed and epigenetic memory. Finally, we use the slow silencing speed and high memory of antiDNMT1 to build a signal duration timer and recorder. These results set the basis for using nanobodies against chromatin regulators for controlling gene expression and epigenetic memory.

Suggested Citation

  • Mike V. Van & Taihei Fujimori & Lacramioara Bintu, 2021. "Nanobody-mediated control of gene expression and epigenetic memory," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20757-1
    DOI: 10.1038/s41467-020-20757-1
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    Cited by:

    1. Boris Kantor & Bernadette O’Donovan & Joseph Rittiner & Dellila Hodgson & Nicholas Lindner & Sophia Guerrero & Wendy Dong & Austin Zhang & Ornit Chiba-Falek, 2024. "The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. G. Veggiani & R. Villaseñor & G. D. Martyn & J. Q. Tang & M. W. Krone & J. Gu & C. Chen & M. L. Waters & K. H. Pearce & T. Baubec & S. S. Sidhu, 2022. "High-affinity chromodomains engineered for improved detection of histone methylation and enhanced CRISPR-based gene repression," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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