Genome-wide annotation of gene regulatory elements linked to cell fitness
作者： Gersbach Ca , Adkar Ss , Reddy Te , Crawford Ge , Barrera A
DOI: 10.1101/2021.03.08.434470
关键词: Epigenomics 、 Gene expression 、 Gene 、 Cell 、 Phenotype 、 Computational biology 、 Function (biology) 、 Biology 、 Chromatin 、 Genome
摘要: Abstract Noncoding regulatory elements control gene expression and govern all biological processes. Epigenomic profiling assays have identified millions of putative elements, but systematically determining the function each those remains a substantial challenge. Here we adapt CRISPR-dCas9-based epigenomic element screening (CERES) technology to screen >100,000 non-coding defined by open chromatin sites in human K562 leukemia cells for their role regulating essential cellular In an initial containing more than 1 million gRNAs, discovered approximately 12,000 with evidence impact on cell fitness. We validated many hits cells, evaluated cell-type specificity second cancer line, target genes using CERES perturbations combined single RNA-seq. This comprehensive quantitative genome-wide map represents framework extensive characterization noncoding that drive complex phenotypes prioritizing genetic variants likely contribute common traits disease risk.
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