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. 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.