Genetic interaction mapping in mammalian cells using CRISPR interference

Nat Methods. 2017 Jun;14(6):577-580. doi: 10.1038/nmeth.4286. Epub 2017 May 8.


We describe a combinatorial CRISPR interference (CRISPRi) screening platform for mapping genetic interactions in mammalian cells. We targeted 107 chromatin-regulation factors in human cells with pools of either single or double single guide RNAs (sgRNAs) to downregulate individual genes or gene pairs, respectively. Relative enrichment analysis of individual sgRNAs or sgRNA pairs allowed for quantitative characterization of genetic interactions, and comparison with protein-protein-interaction data revealed a functional map of chromatin regulation.

MeSH terms

  • Animals
  • Chromosome Mapping / methods*
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Epistasis, Genetic / genetics*
  • High-Throughput Nucleotide Sequencing
  • Mice
  • Protein Interaction Mapping / methods*