Differential regulation of alternate promoter regions in Sox17 during endodermal and vascular endothelial development

Sox17 gene expression is essential for both endothelial and endodermal cell differentiation. To better understand the genetic basis for the expression of multiple Sox17 mRNA forms, we identified and performed CRISPR/Cas9 mutagenesis of two evolutionarily conserved promoter regions (CRs). The deletion of the upstream and endothelial cell-specific CR1 caused only a modest increase in lympho-vasculogenesis likely via reduced Notch signaling downstream of SOX17. In contrast, the deletion of the downstream CR2 region, which functions in both endothelial and endodermal cells, impairs both vascular and endodermal development causing death by embryonic day 12.5. Analyses of 3D chromatin looping, transcription factor binding, histone modification, and chromatin accessibility data at the Sox17 locus and surrounding region further support differential regulation of the two promoters during the development.

Automated summary

The expression of Sox17 gene is crucial for the differentiation of both endothelial and endodermal cells. The study reveals that two evolutionarily conserved promoter regions (CRs) have different roles in regulating the Sox17 gene. Deletion of CR1 only has a modest effect on lympho-vasculogenesis, while deletion of CR2 impairs both vascular and endodermal development.