Duke University CRISPR work: method to precisely control when genes are turned on and active.

In a press release titled --Pulling the strings of our genetic puppetmasters --, there is discussion of the Duke University paper

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"Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers," Isaac B Hilton, Anthony M D'Ippolito, Christopher M Vockley, Pratiksha I. Thakore, Gregory E Crawford, Timothy E Reddy, Charles A Gersbach. Nature Biotechnology, April 6, 2015. DOI: 10.1038/nbt.3199

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Genetic & Engineering News reports on this recent work at Duke University related to CRISPR:

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Best known as a gene-editing system, CRISPR/Cas9 is also being used to edit the epigenome, turning on specific gene promoters and enhancers. The trick is to silence CRISPR/Cas9’s DNA-cutting mechanism. Instead, the CRISPR/Cas9 machinery is used to deliver an enzyme, an acetyltransferase, which adds artificial epigenetic marks to the DNA packaging proteins known as histones.

Gene-editing technologies have been used in several investigations of transcriptional regulation, but with mixed results. For example, some technologies intended for transcriptional control do not enzymatically modulate the chromatin state. They remodel the epigenome indirectly, and so they do not allow specific epigenetic markers to be evaluated.

A more direct and more potent approach has been described by researchers from Duke University. They report that they have designed a fusion protein of a nuclease null deactivated Cas9 (dCas9) with the catalytic histone acetyltransferase core domain of the human E1A-associated protein p300, a highly conserved acetyltransferase involved in a wide range of cellular processes. They reasoned that recruitment of an acetyltransferase by dCas9 to a genomic target site would directly modulate epigenetic structure.

The Duke scientists introduced their epigenome-editing system April 6 in Nature Biotechnology, in an article entitled, “Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.” The article’s authors indicated that their fusion protein catalyzes acetylation of histone H3 lysine 27 at its target sites, leading to robust transcriptional activation of target genes from promoters and proximal and distal enhancers.

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