H3K27ac in WT and Shh-/-, and Shh-/-;Gli3-/- E10.5 limb buds

Purpose: The response to Hedgehog signaling in the limb is driven by GLI bound enhancers. While most Hh targets in the developing limb bud appear to be regulated by the activity of GLI-repressor, the role of GLI activator in this regulation is unclear. Here we assess the roles of GLI activator and repressor in regulating H3K27ac to activate their enhancers. Methods: ChIP-seq was performed in Embryonic day 10.5 mouse limb buds from WT, Shh-/- and Shh-/-Gli3-/- embryos Results: We found that most GLI binding regions can be activated in the absence of both GLI activator and repressor, while a small subset require GLI activator for activity. These indicate that most GLI enhancers in the limb are regulated by GLI repression. ChIP-sequencing of E10.5 forelimb buds from WT, Shh-/-, and Shh-/-;Gli3-/- embryos. Two biological replicates and one input control were submitted per biological condition.