ZFP36 and ELAVL1 combinatorial binding and regulation. (A) In 3′ UTRs, ZFP36 sites are much closer to ELAVL1 sites containing only AUUUA (pink line) than to ELAVL1 sites containing only CUUUC (purple line). PUM2 (orange), FMR1 (green) and QKI (yellow) are included for reference. In parentheses are the number of sites in the 200-nucleotide window, the number of 3′ UTRs with sites for both ZFP36 and the RBP and the number of 3′ UTRs with sites for the RBP. (B) Conditionally independent correlation between the number of ZFP36 binding sites, the depth normalized number of ELAVL1best binding sites and EGFP-ZFP36-induced changes in mRNA abundance. (C, D) ELAVL1all binding sites containing AUUUA (and not UUUUU or CUUUC) correlate independently at a higher level than ELAVL1all binding sites containing only CUUUC (and not UUUUU or AUUUA). (E) Motifs enriched in overlapping ELAVL1 and ZFP36 binding sites vs motifs enriched in ELAVL1-specific binding sites. (F) Scatter plot of the mean and variance of EGFP-ZFP36-induced changes in expression (on the y-axis, negative values indicate a reduction in EGFP-ZFP36 overexpression) and of ELAVL siRNA-knockdown-induced changes in expression (on the x-axis, positive values indicate a reduction in ELAVL1 knockdown) for genes with both ELAVL1 and ZFP36 sites in the 3′ UTR (red), genes with only ELAVL1 sites in the 3′ UTR (green), genes with neither ELAVL1 nor ZFP36 sites in the 3′ UTR (turquoise) and genes with only ZFP36 sites in the 3′ UTR (purple). The bars represent the variance and the point at which they cross the mean. Hotelling’s T2 score, calculated using the Hotelling R package, and Bonferroni corrected P values are indicated for each category. RBP, RNA-binding protein; siRNA, small interfering RNA; UTR, untranslated region.