Common and distinct functions of mouse Dot1l in the regulation of endothelial transcriptome

Epigenetic mechanisms are mandatory for endothelial cells (ECs) during cardiovascular development. Dot1l-mediated gene transcription in mice is essential for development and function of lymphatic ECs (LECs). The role of Dot1l in development and function of blood ECs (BECs) is unclear. RNA-seq datasets from Dot1l-depleted or -overexpressing BECs and LECs were used to comprehensively analyze regulatory networks of gene transcription and pathways. Dot1l depletion in BECs changed the expression of genes involving cell-to-cell adhesion and immunity-related biological processes. Dot1l overexpression changed the expression of genes involved in different types of cell-to-cell adhesion and angiogenesis-related biological processes. Genes involved in specific tissue development-related biological pathways were altered in Dot1l-depleted BECs and LECs. Vascular endothelial growth factor production-related genes were specifically regulated in BECs by Dot1l. Dot1l overexpression uniquely altered ion transportation-related genes in BECs and immune response regulation-related genes in LECs. Importantly, Dot1l overexpression in BECs led to expression of many genes related to the angiogenesis and mitogen-activated protein kinase signaling pathways. The expression of these genes was unchanged in Dot1l-overexpressing LECs. The findings demonstrate the unique transcriptomic program of ECs and the differential functions of Dot1l in the regulation of gene transcription in BECs and LECs. Overall design: High throughput transcriptome sequencing of Dot1l knock-out or control E15.5 mouse embryo skin BEC and cultured mouse embryonic yolk sac BEC and dermal LEC transduced with empty or Dot1l overexpression vector containing lentivirus.