CRISPR screens have enabled the large-scale assessment of gene function, but most approaches are combined with transcriptional profiling without interrogating how genome edits affect chromatin states. Understanding changes in chromatin accessibility following CRISPR edits will help to dissect how genetic alterations affect phenotypic outcomes. In a paper in Nature Methods, Roh et al. introduce a method for chromatin accessibility profiling that is compatible with pooled CRISPR screens to interrogate sequence–function relationships at regions of interest.
Using whole-genome sequencing, the authors use the double-stranded DNA cytidine deaminase DddA11 — which has a preference to deaminate accessible chromatin — to profile chromatin accessibility by leaving C•G-to-T•A mutational marks across kilobase regions. Because DddA11 does not cleave DNA, the approach is compatible with targeted PCR amplification and long-read sequencing to reach high coverage of genomic loci of interest. This is especially useful for mapping primary cells with limited availability.
