DOT1L Drives Endothelial-to-Mesenchymal Transition and Fibrotic Vascular Remodeling via H3K79 Methylation - PubMed
3 hours ago
- #DOT1L
- #Endothelial-to-mesenchymal transition
- #epigenetic regulation
- DOT1L, a histone H3 lysine 79 (H3K79) methyltransferase, is identified as a key epigenetic regulator of endothelial-to-mesenchymal transition (EndoMT) and fibrotic progression.
- In human umbilical vein endothelial cells (ECs), TGFβ stimulation upregulates DOT1L expression and increases H3K79me2 levels during EndoMT; DOT1L knockdown suppresses fibrosis-associated genes.
- SMAD2 directly binds to the DOT1L promoter, increasing its transcription and promoting H3K79me2 deposition at fibrosis-related gene loci after TGFβ2 stimulation.
- In vivo mouse studies show H3K79me2 accumulation in ECs undergoing EndoMT during bleomycin-induced pulmonary fibrosis.
- Endothelial-specific deletion of Dot1L in mice significantly attenuates fibrotic remodeling, collagen deposition, and mesenchymal marker expression, highlighting its potential as a therapeutic target in fibrotic lung disease.