Genetic Engineering Publications - GEG Tech top picks

In this work, the authors developed a CRISPR screen using ~18,000 single guide RNAs targeting >700 kilobases surrounding the genes NF1, NF2, and CUL3, which are involved in BRAF inhibitor resistance in melanoma. They find that noncoding locations that modulate drug resistance also harbor predictive hallmarks of noncoding function. With a subset of regions at the CUL3 locus, they demonstrate that engineered mutations alter transcription factor occupancy and long-range and local epigenetic environments, implicating these sites in gene regulation and chemotherapeutic resistance. Through their expansion of the potential of pooled CRISPR screens, they provide tools for genomic discovery and for elucidating biologically relevant mechanisms of gene regulation.