Upstream regulators of KLF11 and its mutants. Gene targets significantly regulated by KLF11 and its mutants were analyzed by Ingenuity’s Upstream Regulator Analytic that compares the experimentally derive activation or inhibition of focus molecules to relationships between upstream regulators and target molecules known from published data. For each potential upstream regulator and its targets, a p-value for the degree of overlap between that of the protein under study and a z-score for the activation status are calculated. For our study, a threshold of p < 0.05 and a minimum z-score of +/- 2 were employed. The full results are published in Additional file 6: Table S5 and sample signaling cascades presented for wild type KLF11 (A), A347S (B), and Δ486 (C). No cascades were generated that proved significant for the EAPP mutant although a more permissive criteria of a p-value of less than 0.05 did generate a number of single gene associations listed in Additional file 6: Table S5, including a variety of other KLF proteins, hinting at co-regulation within the KLF family. Many of the upstream regulators, such as PPARG, are previously identified co-regulators of KLF11. While the upstream regulators frequently overlap between wild type and mutant conditions, the end gene targets are unique to each condition. These results suggest that the deregulation of KLF11 from a large number of gene networks is completely dependent on the effective coupling of the transcription factor to its chromatin co-factor system.