The histone methyltransferase Suv39h regulates 3T3-L1 adipogenesis
The histone methyltransferase Suv39h regulates 3T3-L1 adipogenesis
复制标题
DOI：
10.1080/21623945.2020.1795422
复制
发表时间：
2020-01-01
期刊：
影响因子：
3.3
通讯作者：
Shi, Hang
中科院分区：
文献类型：
--
作者：
Jing, Jia;Li, Fenfen;Shi, Hang
我们发现了两种组蛋白甲基转移酶 Suv39h1 和 Suv39h2 在 3T3-L1 脂肪形成过程中的独特表达模式，这两种酶都优先催化 H3K9 二甲基化 (H3K9me2) 和进一步 H3K9 三甲基化 (H3K9me3)（一种转录抑制标记）的形成。 Suv39h1和Suv39h2的表达在3T3-L1分化早期急剧增加，在分化诱导后达到峰值，然后在分化后期下降，表明这两种组蛋白甲基转移酶在脂肪形成中发挥关键作用。事实上，通过慢病毒 shRNA 敲低灭活 Suv39h1 或 Suv39h2 会抑制脂肪生成，而过表达 Suv39h1 则会促进脂肪生成。值得注意的是，在 3T3-L1 细胞中过表达或敲除 Suv39h1 与抗脂肪形成调节因子 Wnt10a 的表达相互变化相关。此外，Wnt10a 敲低很大程度上阻止了 Suv39h1 对脂肪生成的抑制作用，表明 Wnt10a 作为下游靶点介导 Suv39h1 在脂肪生成中的作用。从机制上讲，我们涉及 ChIP、免疫共沉淀和焦磷酸测序分析的综合方法表明，Suv39h1 可能通过 H3K9 甲基化以及与 Wnt10a 启动子处的 DNA 甲基转移酶 1 (DNMT1) 相互作用来调节 Wnt10a 表达，从而导致启动子处的 DNA 甲基化改变。我们得出结论，Suv39h 通过 H3K9me3 和 Wnt10a 启动子处的 DNA 甲基化在表观遗传学上下调 Wnt10a 表达，从而促进脂肪生成。缩写标题：Suv39h 和 3T3-L1 脂肪生成
We discovered a unique expression pattern of two histone methyltransferases Suv39h1 and Suv39h2 during 3T3-L1 adipogenesis, both of which preferentially catalyse the formation of H3K9 dimethylation (H3K9me2) and further H3K9 trimethylation (H3K9me3), a transcriptional repressive mark. The expression of Suv39h1 and Suv39h2 displayed a sharp increase at the early stage of 3T3-L1 differentiation, which peaked after differentiation induction, and then declined towards later stage of differentiation, suggesting a key role for these two histone methyltransferases in adipogenesis. Indeed, inactivating Suv39h1 or Suv39h2 via lentiviral shRNA knockdown inhibited adipogenesis, while overexpressing Suv39h1 promoted adipogenesis. Notably, overexpressing or knocking down Suv39h1 in 3T3-L1 cells was associated with reciprocal changes in the expression of Wnt10a, an anti-adipogenic regulator. Further, Wnt10a knockdown largely prevented the inhibitory effect of Suv39h1 on adipogenesis, indicating Wnt10a as a downstream target mediating Suv39h1's action in adipogenesis. Mechanistically, our comprehensive approaches involving ChIP, co-immunoprecipitation and pyrosequencing analysis demonstrated that Suv39h1 may regulate Wnt10a expression via H3K9 methylation and interaction with DNA methyltransferase 1 (DNMT1) at the Wnt10a promoter, resulting in altered DNA methylation at the promoter. We conclude that Suv39h promotes adipogenesis by epigenetically down-regulating Wnt10a expression via H3K9me3 and DNA methylation at the Wnt10a promoter.Abbreviated title:Suv39h and 3T3-L1 Adipogenesis