Genome-wide maps of chromatin accessibility in response to Hh signaling in mouse embryonic forelimb buds

Purpose: The response to Hedgehog signaling in the limb is driven by GLI bound enhancers and the majority of Hh targets in the developing limb bud are regulated solely by the activity of GLI-repressor. Currently, we do not have a comprehensive understanding of how GLI bound enhancers respond to Hedgehog signaling. The goal of this study is to identify how GLI bound enhancers are regulated by Hedgehog signaling and specifically by GLI-repressor. Methods: ATAC-seq was done in embryonic day 10.5 posterior limb buds from control and Shh-null embryos to identify GLI enhancers that change chromatin accessibility in response to Hedgehog signaling. Results: We found that Hedgehog signaling regulates the chromatin accessibility of a subset of GLI binding regions. This subset of GLI bound enhancers has reduced accessibility in the absence of Hedgehog signaling and largely overlaps with GLI enhancers that also have reduced H3K27ac in the absence of Hedgehog signaling. Overall design: ATAC-sequencing in Shh-/- and WT control posterior E10.5 forelimb buds. Two biological replicates were done for each ATAC experiment.