Kaska Koltowska (Uppsala University)

From chromatin organisation to gene expression in lymphatic endothelial cells

Host: Mara Pitulescu

Switching genes on and off is a fundamental part of development, ensuring that a unique molecular code is set up to orchestrate tissue morphogenesis. Changes in chromatin organisation dictate accessibility to gene regulatory elements and control gene expression. We combined ATAC-seq and Hi-C to characterise chromatin accessibility and 3D architecture in LECs and BECs. We uncovered cell type-specific chromatin organisation at a global level, revealing predominant interactions outside of promoter region in LEC and with promoter BECs. By combining ATAC-seq and Hi-C with single cell RNA-seq we identified regulatory logic for nine genes whose expression is enriched in LECs­­. We used a transgenesis approach to validate the candidates and confirmed that short- and long-range enhancers of tbx1 and mafba can drive expression in the LECs, highlighting the potential of our combinatory approach. We focused on the known lymphatic regulator mafba and reconstructed its tissue-specific regulatory networks by identifying downstream targets using TF footprinting. Overall, our work provides powerful muliti-omic datasets, that can be used to systematically determine the regulatory networks governing LECs identity.

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