DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium

• CAGE RNA sequencing identifies transcription factors activated by VEGFR-3
• MAFB is a lymphatic transcription factor specifically activated by VEGFR-3
• MAFB controls the expression of other transcription factors and lymphatic marker genes
• MAFB-deficient mice show abnormal lymphatic patterning in the skin

SummaryVEGF-C/VEGFR-3 signaling plays a central role in lymphatic development, regulating the budding of lymphatic progenitor cells from embryonic veins and maintaining the expression of PROX1 during later developmental stages. However, how VEGFR-3 activation translates into target gene expression is still not completely understood. We used cap analysis of gene expression (CAGE) RNA sequencing to characterize the transcriptional changes invoked by VEGF-C in LECs and to identify the transcription factors (TFs) involved. We found that MAFB, a TF involved in differentiation of various cell types, is rapidly induced and activated by VEGF-C. MAFB induced expression of PROX1 as well as other TFs and markers of differentiated LECs, indicating a role in the maintenance of the mature LEC phenotype. Correspondingly, E14.5 Mafb−/− embryos showed impaired lymphatic patterning in the skin. This suggests that MAFB is an important TF involved in lymphangiogenesis.

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