Extended Data Fig. 8: RBFOX2 regulation of m6A is not significantly related to its role in regulating alternative splicing.

a, Functional enrichment analysis of genes with their promoters bound by RBFOX2 and marked with both H3K4me3 and m6A. Inset boxplot shows gene expression level log2FC comparing RBFOX2 KD with control K562 cells. Genes with RBFOX2 binding and H3K4me3 modification were categorized into two subgroups according to whether they were marked with m6A (+) or not (−). n = 2 biologically independent samples. RBFOX2 binding are from ENCODE project, and m6A MeRIP-seq and H3K4me3 ChIP-seq are from this study. b, Enrichment analysis of alternatively spliced genes upon RBFOX2 knockdown in K562 cells. c-d, Enrichment analysis of RBFOX2 bound and alternatively spliced genes upon RBFOX2 knockdown in K562 cells. Alternatively spliced genes bound by RBFOX2 were categorized into two groups according to whether those genes were methylated by m6A (RBFOX2(+) m6A(+)) or not (RBFOX2(+) m6A(−)). e, Enrichment analysis of genes harboring both RBFOX2 binding and m6A methylation, but which were not alternatively spliced upon RBFOX2 knockdown in K562 cells. f, Barplot showing the ratios of alternatively spliced genes by RBFOX2 knockdown in NB4 cells. g, Enrichment analysis of alternatively spliced genes upon RBFOX2 knockdown in NB4 cells. h-i, Enrichment analysis of RBFOX2 bound and alternatively spliced genes upon RBFOX2 knockdown in NB4 cells. RBFOX2 bound and alternatively spliced genes were categorized into two groups according to whether those genes were methylated by m6A (RBFOX2(+) m6A(+)) or not (RBFOX2(+) m6A(−)). j, Enrichment analysis of genes harboring both RBFOX2 binding and m6A methylation, but which were not alternatively spliced upon RBFOX2 knockdown in NB4 cells. For b-e and g-j, one-sided P values were calculated using Fisher’s Exact test, and the size of the circle represents the level of significance, with larger circles indicating greater significance and smaller circles indicating lower significance.