ArticleNature biomedical engineering2024
Genome-wide Cas9-mediated screening of essential non-coding regulatory elements via libraries of paired single-guide RNAs.
Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Towards efficient perturbation for the noncoding genome.Nature communications · 2026Article
- Fluid shear stress activates a targetable mechano-metastatic cascade to promote medulloblastoma metastasis.Nature biomedical engineering · 2026Article
- Systematic analysis of functional genetic and epigenetic variants in colorectal cancer.Science advances · 2026Article
- ePerturbDB: enhancer's experimental perturbation database.Database : the journal of biological databases and curation · 2026Article
- Engineering structural variants to interrogate genome function.Nature genetics · 2024Review
- Discovering the hidden function in fungal genomes.Nature communications · 2024Review
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16 authors.
Funding
Abstract
The functions of non-coding regulatory elements (NCREs), which constitute a major fraction of the human genome, have not been systematically studied. Here we report a method involving libraries of paired single-guide RNAs targeting both ends of an NCRE as a screening system for the Cas9-mediated deletion of thousands of NCREs genome-wide to study their functions in distinct biological contexts. By using K562 and 293T cell lines and human embryonic stem cells, we show that NCREs can have redundant functions, and that many ultra-conserved elements have silencer activity and play essential roles in cell growth and in cellular responses to drugs (notably, the ultra-conserved element PAX6_Tarzan may be critical for heart development, as removing it from human embryonic stem cells led to defects in cardiomyocyte differentiation). The high-throughput screen, which is compatible with single-cell sequencing, may allow for the identification of druggable NCREs.
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