Extended Data Fig. 3: RBFOX2 recruits m6A MTC to gene promoter for RNA methylation installation.
a, RBFOX2 expression in K562 cells. b, H3K4me3 level changes at H3K4me3 peaks (N) by RBFOX2 KD in K562 cells. H3K4me3 peak regions were categorized into six groups based their overlap with RBFOX2 or m6A. From left to right, N = 9767, 11201, 14907, 3706, 3884,178. c, Correlation of log2FC between m6A level and caRNA abundance by RBFOX2 KD in K562 cells. P value by PCC. d, The elongation rate changes comparing RBFOX2 KD with control K562 cells. Transcripts (N) were categorized into three groups based on their overlap with RBFOX2 or m6A. From left to right, N = 130274, 13232, and 5678. e, In situ PLA detecting the close proximity (green) between RBFOX2 and METTL3 or METTL14 in K562 cells. Scale bar, 5μM. f, The binding intensity of METTL3 and METTL14 at m6A, RBFOX2 and RBM15 marked promoter regions, respectively. g, Distribution of RBM15 (eCLIP) or RBFOX2 (ChIP) peaks at distinct genomic regions annotated by HOMER (K562, left panel). Functional enrichment analysis of genes bound by both RBFOX2 and RBM15 (K562, right panel). One-sided P value by Fisher’s Exact test. h, m6A methylation level on peaks (N) occupied by either RBFOX2 or RBM15 (K562). From left to right, N = 10064, 1322 and 3187. i, Venn diagram of peak overlap between RBFOX2 (ChIP-seq) and RBM15 (eCLIP) in K562 cells (left panel). Here RBFOX2 and RMB15 peaks were required to overlap with caRNA m6A peaks. Barplot showing the proportion of m6A peaks (RBM15 bound versus unbound) that overlap with RBFOX2 peaks (right panel). Two-sided P value was calculated by Fisher’s exact test. j, m6A log2FC at m6A peak regions (N, RBM15 bound versus unbound) in RBFOX2 KD versus control K562 cells. From left to right, N = 26110 and 2360. k, RBM15 expression in K562 cells. l, Average profile of RBFOX2 binding intensity at RBFOX2 peaks (K562). The depicted genome-wide data represent an integration of all samples, including two biologically independent replicates.
