Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China; Laboratory of Animal Biotechnology and Breeding, College of Animal Science and Veterinary Medicine, Xinyang College of Agriculture and Forestry, Xinyang, Henan 464000, China.
Laboratory of Animal Biotechnology and Breeding, College of Animal Science and Veterinary Medicine, Xinyang College of Agriculture and Forestry, Xinyang, Henan 464000, China.
Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Feb;1863(2):132-142. doi: 10.1016/j.bbalip.2017.11.001. Epub 2017 Nov 11.
Methionine adenosyltransferase (MAT) is a critical biological enzyme and that can catalyze L-met and ATP to form S-adenosylmethionine (SAM), which is acted as a biological methyl donor in transmethylation reactions involving histone methylation. However, the regulatory effect of methionine adenosyltransferase2A (MAT2A) and its associated methyltransferase activity on adipogenesis is still unclear. In this study, we investigate the effect of MAT2A on adipogenesis and its potential mechanism on histone methylation during porcine preadipocyte differentiation. We demonstrated that overexpression of MAT2A promoted lipid accumulation and significantly up-regulated the levels of adipogenic marker genes including PPARγ, SREBP-1c, and aP2. Whereas, knockdown of MAT2A or inhibition MATII enzyme activity inhibited lipid accumulation and down-regulated the expression of the above-mentioned genes. Mechanistic studies revealed that MAT2A interacted with histone-lysine N-methyltransferase Ezh2 and was recruited to Wnt10b promoter to repress its expression by promoting H3K27 methylation. Additionally, MAT2A interacted with MafK protein and was recruited to MARE element at Wnt10b gene. The catalytic activity of MAT2A as well as its interacting factor-MAT2B, was required for Wnt10b repression and supplying SAM for methyltransferases. Moreover, MAT2A suppressed Wnt10b expression and further inhibited Wnt/β-catenin signaling to promote adipogenesis.
甲硫氨酸腺苷转移酶（MAT）是一种关键的生物酶，可催化 L-甲硫氨酸和 ATP 形成 S-腺苷甲硫氨酸（SAM），后者作为生物甲基供体在涉及组蛋白甲基化的转甲基反应中发挥作用。然而，甲硫氨酸腺苷转移酶 2A（MAT2A）及其相关甲基转移酶活性对脂肪生成的调节作用尚不清楚。在这项研究中，我们研究了 MAT2A 对猪前体脂肪细胞分化过程中脂肪生成的影响及其对组蛋白甲基化的潜在机制。我们证明，MAT2A 的过表达促进了脂质积累，并显著上调了脂肪生成标记基因，包括 PPARγ、SREBP-1c 和 aP2 的水平。相反，MAT2A 的敲低或 MATII 酶活性的抑制抑制了脂质积累，并下调了上述基因的表达。机制研究表明，MAT2A 与组蛋白赖氨酸 N-甲基转移酶 Ezh2 相互作用，并被募集到 Wnt10b 启动子，通过促进 H3K27 甲基化来抑制其表达。此外，MAT2A 与 MafK 蛋白相互作用，并被募集到 Wnt10b 基因的 MARE 元件。MAT2A 的催化活性及其相互作用因子 MAT2B，对于 Wnt10b 的抑制以及为甲基转移酶提供 SAM 都是必需的。此外，MAT2A 抑制 Wnt10b 的表达，进一步抑制 Wnt/β-catenin 信号通路，从而促进脂肪生成。
