Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases

Figure 1 Landscape of the enhances in the kidney and topological chromatin domains around the BMP7 locus. Exons and introns of the genes within the locus (chr2: 172,250,000-172,850,000 mm9) are represented by blue boxes and arrowed dashes, respectively. Names of the genes are indicated above or below the respective boxes. The ChIP-seq signals of H3K27ac in the kidney tissue at different stages [E14.5, E15.5, E16.5, postnatal day (P)0 and 8-wk-old; indicated to the right] are shown with pink plots. H3K4me1 and H3K27me3 signals in the adult kidney are shown with green and red plots, respectively. The ChIP-seq data were obtained from the ENCODE project[48]; the Data Coordination Consortium accession numbers are ENCSR703ZPF, ENCSR000CAF and ENCSR000CFP for H3K27ac, H3K4me1 and H3K27me3, respectively. Enhancer candidates are represented by pink ovals at the bottom: The RV enhancer is bound by Six2 and β-catenin, and induces reporter expression in the Six2- compartment of the renal vesicle[45]; the intron 1 enhancer drives reporter expression in the developing ureteric buds[43]; the Six2 binding site next to the intron 1 enhancer was identified by ChIP-seq[45] but is not sufficient to induce gene expression in the developing kidney[43]. Note that the H3K27ac mark around the intron 1 enhancer during embryogenesis diminishes in the adult stage. The chromatin domains identified by 4C-seq are shown at the top (indicated by whiskered lines), together with the actual results of the 4C-seq that are shown below[42]. The viewpoints of the 4C-seq are indicated by arrows on the plots: Tfap2c promoter (blue), transition zone (TZ; gray), next to TZ in the BMP7 domain (yellow), and BMP7 promoter (green). The European Nucleotide Archive accession number of the 4C-seq data is ERP005557[42]. The TZ between the two domains is indicated by the purple rectangle that spans the entire diagram.