Skip to main content
Figure 1 | BMC Molecular Biology

Figure 1

From: Single and combinatorial chromatin coupling events underlies the function of transcript factor krüppel-like factor 11 in the regulation of gene networks

Figure 1

KLF11-mediated gene expression is disrupted in the presence of chromatin coupling mutations. (A) KLF11 is 495 amino acids and contains a highly conserved C-terminal C2H2 zinc finger domain. Known chromatin coupling domains explored here are highlighted. (B) Panc1 epithelial cells were transfected with wild type KLF11 and chromatin immunoprecipitation performed and hybridized to a whole genome promoter array. The frequency of identified peaks 5 kb upstream and downstream of known transcription start sites were binned according to distance. The majority of KLF11 binding sites were 500–1000 base pairs from transcription start sites. (C) Gene ontological analysis of KLF11-bound targets reveals enrichment of genes in known KLF11-associated biological processes, including immune response, TOR signaling, and insulin sensitivity. For whole genome analysis, mutants were designed against three of the previously characterized chromatin coupling domains. The EAPP mutation in the N-terminus decouples the Sin3/histone deacetylase system. The A347S mutation in the proline rich domain decouples KLF11 from WD40 containing proteins. Finally, the deletion mutation starting at amino acid 486 disconnects KLF11 from the HP1/histone methyltransferase system. Panc1 cells were transduced with empty vector, wild type KLF11 or the A347S, Δ486, or EAPP mutants. Whole genome transcriptional profiling was performed. The criteria for significant regulation over empty vector was set at a threshold of +/- 1.5 log2 fold change and a p-value with false discovery rate of less than 0.05. For the EAPP mutant, the p-value did not include false discovery rate thresholding due to the limited experimental effects of this mutant. (D) 75 genes were significantly regulated by KLF11 overexpression (p < 0.05) and are directly bound by KLF11 as determined by chromatin immunoprecipitation. Examination of effects of the three chromatin decoupling mutants reveals that expression is frequently altered in the presence of one or more of these variants.

Back to article page