Transcriptional control of Sulf1 by WT1 primes epicardial signalling and fate by modifying extracellular heparan sulfate status [ATAC-Seq]

Considering the transcriptional correlations we observed between WT1 and 6-O-endosulfatases in the epicardium, we sought to elucidate whether WT1 regulates 6-O-endosulfatase expression directly and how its binding may differ between Sulf1 and Sulf2 in the epicardium. We first assessed the landscape of chromatin accessibility in FACS sorted epicardial cells at E13.5 (CD31-tdTomato+PDPN+), and employed TOBIAS footprinting to identify candidate WT1 binding sites in the Sulf1 and Sulf2 loci. This analysis predicted WT1 binding to the highly accessible Sulf1 promoter but no binding was predicted for Sulf2. As expected, there was lower accessibility in this locus which reflected reduced Sulf2 gene activity in the epicardial layer.