Transcriptional control of Sulf1 by WT1 primes epicardial signalling and fate by modifying extracellular heparan sulfate status [CUT&Run]

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 employed CUT&RUN-seq experiments that mapped genome-wide binding sites of WT1 and histone modifications in cultured epicardial cells (MEC1). We identified weak, although variable, binding of WT1 to the Sulf1 promoter and significant WT1 binding to an intronic enhancer, marked by active chromatin modification H3K27ac, located in intron 1 of the Sulf1 gene. Interestingly, the CUT&RUN-seq experiments also revealed significant binding of WT1 to the third intron of the Sulf2 gene, displaying chromatin accessibility without any histone marks or gene activity.