叉头框蛋白M1（FOXM1）通过SET7-组蛋白H3第4位赖氨酸单甲基化（H3K4me1）-脂肪酸合酶（FASN）轴维持脂肪酸稳态。

FOXM1 maintains fatty acid homoeostasis through the SET7-H3K4me1-FASN axis.

作者信息

Li Xixi, Su Weijie, Wu Honglin, Xu Jiakun, Tang Hongxing, Chen Xiangkun, Yin Zhanqi, Zhang Changming, Yang Jia, Yang Yibing, Zhang Nu, Yang Lixuan

机构信息

Neurosurgery Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Intensive Care Unit, The First people's Hospital of Suqian City, Jiangsu Province, Suqian, China.

出版信息

Cell Death Discov. 2023 Aug 24;9(1):310. doi: 10.1038/s41420-023-01540-9.

Reprogramming of metabolic genes and subsequent alterations in metabolic phenotypes occur widely in malignant tumours, including glioblastoma (GBM). FOXM1 is a potent transcription factor that plays an oncogenic role by regulating the expression of many genes. As a SET domain containing protein, SET7 is a protein lysine methyltransferase which monomethylates histone proteins and other proteins. The epigenetic modification of histones regulates gene expressions by epigenetically modifying promoters of DNAs and inter vening in tumor development. Activation of FASN increased de novo fatty acid (FA) synthesis, a hallmark of cancer cells. Here, we report that FOXM1 may directly promote the transcription of SET7 and activate SET7-H3K4me1-FASN axis, which results in the maintenance of de novo FA synthesis.

代谢基因的重编程以及随后代谢表型的改变在包括胶质母细胞瘤（GBM）在内的恶性肿瘤中广泛存在。FOXM1是一种强效转录因子，通过调控许多基因的表达发挥致癌作用。作为一种含SET结构域的蛋白，SET7是一种蛋白赖氨酸甲基转移酶，可使组蛋白和其他蛋白发生单甲基化。组蛋白的表观遗传修饰通过对DNA启动子进行表观遗传修饰并参与肿瘤发展来调节基因表达。脂肪酸合酶（FASN）的激活增加了脂肪酸（FA）的从头合成，这是癌细胞的一个标志。在此，我们报道FOXM1可能直接促进SET7的转录并激活SET7-H3K4me1-FASN轴，从而维持FA的从头合成。