Creative Research Initiatives Center for Epigenetic Code and Diseases, Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, Republic of Korea.
Biochem Biophys Res Commun. 2020 May 21;526(1):176-183. doi: 10.1016/j.bbrc.2020.03.058. Epub 2020 Mar 20.
Autophagy is an essential process to maintain cell survival and homeostasis under various stress conditions. Here, we report that lysine-specific demethylase 3A (KDM3A) plays an important role in starvation-induced autophagy. Using Kdm3a knockout mice, we demonstrate that KDM3A is crucial for proper hepatic autophagy in vivo. Hepatic mRNA expression analysis and ChIP assay in WT and Kdm3a knockout mouse livers reveal that KDM3A activates autophagy genes by reducing histone H3K9me2 levels upon fasting. Together, our finding represents previously unidentified function of KDM3A as a key regulator of autophagy, implicating potential therapeutic approaches for autophagy-related diseases.
自噬是细胞在各种应激条件下维持生存和内稳态的必要过程。在这里,我们报告赖氨酸特异性去甲基化酶 3A(KDM3A)在饥饿诱导的自噬中发挥重要作用。使用 Kdm3a 敲除小鼠,我们证明 KDM3A 在体内对肝脏自噬至关重要。WT 和 Kdm3a 敲除鼠肝脏的肝 mRNA 表达分析和 ChIP 分析显示,KDM3A 通过在禁食时降低组蛋白 H3K9me2 水平来激活自噬基因。总之,我们的发现代表了 KDM3A 作为自噬关键调节剂的先前未被识别的功能,为自噬相关疾病的潜在治疗方法提供了依据。