Distinct global shifts in genomic binding profiles of limb malformation-associated HOXD13 mutations

Gene regulation by HOXD13^Q317K is more similar to PITX1 than to HOXD13^wt or HOXD13^Q317R. Global expression analysis of genes regulated by HOXD13^wt, HOXD13^Q317R, HOXD13^Q317K, or PITX1 in chMM cultures. RNA-seq expression analysis found 3118 transcripts (2506 genes) to be at least twofold differentially regulated in Hoxd13^wt, Hoxd13^Q317R, Hoxd13^Q317K, or PITX1 chMM compared to mock-infected cultures (RPKM cutoff 2). (A) Principle component analysis (PCA) of the expression values (normalized to expression values in mock-infected cultures) of these genes shows a similar clustering as seen in the ChIP-seq PCA. (B) Hierarchical clustering of the expression values (RPKM) clusters Hoxd13^Q317K with PITX1 and Hoxd13^Q317R with Hoxd13^wt. Red indicates up-regulation and green indicates down-regulation, as compared to mock-infected cultures.