Researchers interested in untangling the functional roles of regulatory elements have a new screening tool at their disposal: a CRISPR-Cas9-based epigenomic editing scheme.
In a study appearing online [April 3] in Nature Biotechnology, Duke University researchers introduced a strategy known as “CRISPR-Cas9-based epigenomic regulatory element screening,” or CERES, designed for profiling regulatory elements in a high-throughput manner in a native chromosome context. By using CERES in screens for gain- or loss-of-regulatory element function in a handful of human cell lines, for example, they narrowed in on new and known expression regulators at the beta-globin and HER2 loci.
“Ultimately, we envision that these methods will provide information on how altered regulation of gene expression contributes to disease, drug response, and regeneration,” co-corresponding authors Charles Gersbach, Timothy Reddy, and Gregory Crawford, and their co-authors wrote.
“Because screening with epigenome editing perturbs regulatory element activity directly rather than via DNA mutation, the approach offers several advantages over genome editing screens,” the authors wrote, noting that “use of the [KRAB and p300-fused Cas9 constructs] in parallel screens around the same loci uniquely facilitates the identification of elements that are necessary and sufficient, respectively, for target gene expression.”
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