Histone methyltransferase SETDB1 inhibits TGF-β-induced epithelial–mesenchymal transition in pulmonary fibrosis by regulating SNAI1 expression and the ferroptosis signaling pathway

• DOI: 10.1016/j.abb.2021.109087
• Publication Date: 2021-11-18T07:47:20Z
• Authors: Tiantian Liu; Pengli Xu; Shaorui Ke; Haoran Dong; Mengmeng Zhan; Qin Hu; Jiansheng Li
• Keywords: SNAI1; Chromatin immunoprecipitation; Demethylase; Histone Methylation; Reprogramming

The epithelial–mesenchymal transition (EMT) is an important pathological process in the occurrence of pulmonary fibrosis. Changes histone methylation modifications key genes play role this process. As a methyltransferase, regulatory mechanism and SET domain bifurcated 1 (SETDB1) fibrosis remain unclear. We found that SETDB1 inhibited EMT cells attenuated expression to relieve inhibition during transforming growth factor-β (TGF-β)-induced EMT. Silencing significantly enhanced mesenchymal phenotype induced by TGF-β deposition fibronectin reduced E-cadherin. decrease E-cadherin induction led increased lipid reactive oxygen species (ROS) ferrous ions, which ferroptosis. Chromatin immunoprecipitation (ChIP) results showed regulates Snai1 catalyzing H3 lysine 9 trimethylation (H3K9me3) Snai1, main transcription factor initiates EMT, thus, indirectly Surprisingly, when examining effect overexpressed on we alleviated also caused suggest overexpression partially reverses epithelial state, while those fail reverse are depleted In conclusion, methylase epigenetically, driving gene reprogramming ferroptosis response TGF-β. However, there unexplored links between epigenetic transcriptional processes regulate TGF-β-dependent manner.