DOT1L enhances BLM-induced pulmonary fibrosis by inducing endothelial-to-mesenchymal transition via H3K79me2 [ChIP-seq]

Here, we showed that induction of EndoMT activated DOT1L expression and enhanced H3K79me2 level by TGFβ2 in human umbilical vein endothelial cells (HUVECs) in vitro. Using a bleomycin (BLM)-induced idiopathic pulmonary fibrosis (IPF) model, endothelial-lineage tracing reporter mice, and endothelial-specific Dot1L knockout mice, we confirmed that DOT1L mediates EndoMT and drives pulmonary fibrosis in vivo through H3K79 methylation.

ChIP-seq revealed direct binding of SMAD2/3 to the DOT1L promoter and increased H3K79me2 deposition at fibrosis-related genes following TGFβ2 stimulation.