Figure 7. Functional analysis of TF co-occupancy at MK enhancers.

(a) Composite ChIP-seq signals for NF-E2, FLI1, RUNX1, and H3K4me2 at 3 distinct clusters of NF-E2 binding sites, identified by K-means clustering of binding sites for the three TFs and described in the text. (b) Composite ChIP-seq signals for H3K4me2 in MK_Imm and MK_Mat at the 3 clusters of NF-E2 binding sites. (c) ChIP-seq data traces at a representative MK_Mat-specific locus, Itgb3, showing all three TFs occupying a putative regulatory region marked with H3K4me2. Other sites in the locus show binding of one or two TFs. (d) Odds ratios of genes near (<20 kb) NF-E2 binding sites in each cluster showing higher expression in MK_Mat (blue) or in MK_Imm (red), relative to the genome background. (e) Proportion of genes with nearby binding of the various combinations of NF-E2, FLI1, and RUNX1 among genes showing higher expression in MK_Mat. The data indicate the functional role of FLI1, in conjunction with NF-E2 or RUNX1 and especially with both TFs, in regulating genes expressed in mature, but not in immature (Suppl. Fig. 2d) MK.