Genome-Scale Exon Perturbation Screens Uncover Critical Exons for Cell Fitness [ChIP-seq]
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ABSTRACT: Although CRISPR-Cas technology has revolutionized functional genomics_the systematic exploration of the role of individual exons for critical cellular phenotypes is lagging_limiting our understanding of genome regulation. To overcome this constraint_we have optimized and applied massively parallel exon deletion and splice site mutation screens in human cell lines identifying thousands of exons required for cell fitness. Fitness-promoting exons are enriched in essential and highly expressed genes and frequently overlap protein domains and interaction interfaces. In contrast_fitness-suppressing exons that are enriched in low-expressed_non-essential genes and tend to overlap intrinsically disordered regions. In-depth mechanistic investigation of a screen hit_TAF5 alternative exon-8_reveals that its inclusion controls the assembly of the TFIID general transcription initiation complex regulating gene expression outputs. Collectively_by applying orthogonal exon perturbation screening strategies we have generated a resource of phenotypically important exons and uncovered mechanisms that control gene expression and cell fitness.
ORGANISM(S): Homo sapiens
PROVIDER: GSE244373 | GEO | 2024/06/24
REPOSITORIES: GEO
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