Figure 8

The Grem1 genomic landscape harbours multiple distant cis -regulatory regions that orchestrate Grem1 transcription in limb buds. Mapping of the DNAse I hypersensitive (HS) sites in fore-, hindlimb bud and trunk mesoderm of mouse embryos at E11.5 (ENCODE Group, University of Washington, [33, 34]). A schematic representation of the cis-regulatory landscape that regulates Grem1 expression in the limb bud mesenchyme is shown below the HS site tracks. Interestingly, the major HS sites co-localise with regions that are functionally required, highly conserved (HMCO1-3, blue), and/or overlap with experimentally defined GBRs (red, ref. [32] and this study) or a CTCF binding region (green, [31]). Red arrowheads indicate consensus GLI binding sites identified by in silico analysis. HMCO1 and HMCO2 overlap with limb bud specific HS sites, while HMCO3 overlaps with a trunk mesodermal HS site. For exact coordinates, see Additional file 8.