Fig. 2

Functional screen of HRR-associated enhancers in melanoma. a Functional evaluation of HRR-associated enhancer in A375 public CRISPR KO positive selection screen. Scatter plot represents the most significant presumed target genes of HRR-associated enhancers in CRISPR positive selection results, presumed targets were defined as genes within 1 Mb upstream and downstream of enhancers; box plot represents the difference of CRISPR enrichment scores between the presumed genes in HRR-associated enhancer across 5 HRR types group and those in HRR-unrelated enhancer group, Mann–Whitney U test (p-value DEL = 0.0033; p-value DUP = 0.0028; p-value SNV = 0.0076). b Pipeline for selecting HRR-associated enhancer core regions, CRISPRi sgRNA library design and screening workflow. c CRISPRi screen result at enhancer level, a total of 66 functional enhancers with FDR < 0.05 were highlighted. Details about the top 20 enhancers are shown on the right table. d Annotation of candidate target genes of the functional enhancers according to H3K27ac HiChIP loops, genes are labeled by colors according to different evidence sources (purple: genetic evidence, green: functional evidence, blue: literature evidence, and yellow: other cancer driver genes, annotation resource see “Methods” for details). e CRISPRi screen result at sgRNA level, the sgRNA enrichment diagrams were shown for the top 4 significant enhancers