ArticleCell genomics2024
SpRY-mediated screens facilitate functional dissection of non-coding sequences at single-base resolution.
Article in Cell genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Constructing an Adenine Base Editor inMicroorganisms · 2026Article
- Decoding thebioRxiv : the preprint server for biology · 2026Article
- Dissecting cellular ecosystem with single-cell CRISPR screens.Blood science (Baltimore, Md.) · 2025Article
- Endogenous fine-mapping and prioritization of functional regulatory elements in complex genetic loci.Cell genomics · 2025Article
- Fueling chromosomal gene diversification and artificial evolution with CRISPR.Genome biology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CRISPR mutagenesis screens conducted with SpCas9 and other nucleases have identified certain cis-regulatory elements and genetic variants but at a limited resolution due to the absence of protospacer adjacent motif (PAM) sequences. Here, leveraging the broad targeting scope of the near-PAMless SpRY variant, we have demonstrated that saturated SpRY mutagenesis and base editing screens can faithfully identify functional regulatory elements and essential genetic variants for target gene expression at single-base resolution. We further extended this methodology to investigate a genome-wide association study (GWAS) locus at 10q22.1 associated with a red blood cell trait, where we identified potential enhancers regulating HK1 gene expression, despite not all of these enhancers exhibiting typical chromatin signatures. More importantly, our saturated base editing screens pinpoint multiple causal variants within this locus that would otherwise be missed by Bayesian statistical fine-mapping. Our approach is generally applicable to functional interrogation of all non-coding genomic elements while complementing other high-coverage CRISPR screens.
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