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

• Published in: iScience 2022-09, Vol.25 (9), p.104905, Article 104905
• Main Authors: Trinh, Linh T., Osipovich, Anna B., Sampson, Leesa, Wong, Jonathan, Wright, Chris V.E., Magnuson, Mark A.
• Format: Article
• Language: English
• Subjects: Developmental biology; Developmental genetics; Embryology; Genetics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.104905

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. [Display omitted] •Two Sox17 conserved regions (CR1/CR2) are differentially active during embryogenesis•CR1 deletion increases lympho-vasculogenesis by reducing Sox17 and Notch signaling•CR2 deletion lethally impairs hepatopancreatobiliary and vascular development•Transcription factors bind at CR1 and a distal element interacts with CR2 Genetics; Developmental genetics; Developmental biology; Embryology