Protein arginine methyltransferase 1 (PRMT1) methylates a variety of histone and nonhistone protein substrates to regulate multiple cellular functions such as transcription, DNA damage response, and signal transduction. It has been reported as an emerging regulator of various metabolic pathways including glucose metabolism in the liver, atrophy in the skeletal muscle, and lipid catabolism in the adipose tissue. However, the underlying mechanisms governing how PRMT1 regulates adipogenesis remain elusive. Here, we delineate the roles of PRMT1 in mitotic clonal expansion and adipocyte differentiation. Gain and loss of functions demonstrate that PRMT1 is essential for adipogenesis of 3T3-L1 and C3H10T1/2 cells. Mechanistically, we show PRMT1 promotes the expression of transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) by catalyzing histone modification H4R3me2a and impedes the activation of Wnt/β-catenin signaling by increasing the level of Axin to accelerate adipogenic differentiation. In addition, we demonstrate mitotic clonal expansion is suppressed by PRMT1 deficiency. PRMT1 interacts with transcription factor CCATT enhancer-binding protein β (C/EBPβ), and the absence of PRMT1 leads to the depressed phosphorylation of C/EBPβ. Interestingly, we discover PRMT1 acts as a positive regulator of C/EBPβ protein stability through decreasing the level of E3 ubiquitin ligase Smurf2, which promotes the ubiquitination and degradation of C/EBPβ, thus facilitating adipogenesis. Collectively, these discoveries highlight a critical role of PRMT1 in adipogenesis and provide potential therapeutic targets for the treatment of obesity.

蛋白质精氨酸甲基转移酶 1 (PRMT1) 甲基化多种组蛋白和非组蛋白底物以调节多种细胞功能，例如转录、DNA 损伤反应和信号转导。据报道，它是各种代谢途径的新兴调节剂，包括肝脏中的葡萄糖代谢、骨骼肌中的萎缩和脂肪组织中的脂质分解代谢。然而，控制 PRMT1 如何调节脂肪生成的潜在机制仍然难以捉摸。在这里，我们描述了 PRMT1 在有丝分裂克隆扩增和脂肪细胞分化中的作用。功能的获得和丧失表明 PRMT1 对于 3T3-L1 和 C3H10T1/2 细胞的脂肪生成至关重要。机械地，我们显示 PRMT1 通过催化组蛋白修饰 H4R3me2a 促进转录因子过氧化物酶体增殖物激活受体-γ (PPARγ) 的表达，并通过增加 Axin 的水平来阻止 Wnt/β-catenin 信号传导的激活以加速脂肪形成分化。此外，我们证明 PRMT1 缺陷会抑制有丝分裂克隆扩增。PRMT1 与转录因子 CCATT 增强子结合蛋白 β (C/EBPβ) 相互作用，PRMT1 的缺失导致 C/EBPβ 的磷酸化降低。有趣的是，我们发现 PRMT1 通过降低 E3 泛素连接酶 Smurf2 的水平作为 C/EBPβ 蛋白稳定性的正调节因子，促进 C/EBPβ 的泛素化和降解，从而促进脂肪生成。集体，