KLF11 regulates gene expression through combinatorial and singular chromatin coupling events. (A) The A347S mutant, which decouples KLF11 from WD40 proteins, displays the most genome wide effects, uniquely affecting the expression of 708 genes, whereas the (B) Δ486 deletion mutation (decouples KLF11 from HP1/histone methyltransferases) and the (C) EAPP mutation (decouples KLF11 from binding the Sin3 scaffold protein and subsequently histone deacetylases) uniquely regulate only 44 and 21 genes, respectively. (D) Examination of the overlap between genes significantly regulated by the A347S mutant reveals that approximately 50% are regulated in a similar fashion to the Δ486 mutant, although with varying degrees of intensity. The EAPP mutant, however, displays near complete reversal of these targets. (E) Wild type KLF11 and the A347S mutant share 411 targets apart from either the EAPP or Δ486 mutants, although (F) 352 targets exists that are shared between all three systems. These data indicate that KLF11 chromatin coupling occurs in a largely combinatorial fashion. (G) Only 14 genes were identified that are uniquely regulated by KLF11, independent of chromatin coupling to the transcription factor. Ontological analysis of these genes reveals roles in cancer, cellular proliferation, and metabolism.