G-quadruplex structure (G4) is a type of DNA secondary structure that widely exists in the genomes of many organisms. G4s are believed to participate in multiple biological processes. Acyl-CoA binding protein (ACBP), a ubiquitously expressed and highly conserved protein in eukaryotic cells, plays important roles in lipid metabolism by transporting and protecting acyl-CoA esters. Here, we report the functional identification of a G4 in the promoter of the ACBP gene in silkworm and human cancer cells. We found that G4 exists as a conserved element in the promoters of ACBP genes in invertebrates and vertebrates. The BmACBP G4 bound with G4-binding protein LARK regulated BmACBP transcription, which was blocked by the G4 stabilizer pyridostatin (PDS) and G4 antisense oligonucleotides. PDS treatment with fifth instar silkworm larvae decreased the BmACBP expression and triacylglycerides (TAG) level, resulting in reductions in fat body mass, body size and weight and growth and metamorphic rates. PDS treatment and knocking out of the HsACBP G4 in human hepatic adenocarcinoma HepG2 cells inhibited the expression of HsACBP and decreased the TAG level and cell proliferation. Altogether, our findings suggest that G4 of the ACBP genes is involved in regulation of lipid metabolism processes in invertebrates and vertebrates.

中文翻译：

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DNA G-四链体结构通过酰基辅酶 A 结合蛋白参与脂质代谢调控

G-四链体结构（G4）是一种广泛存在于许多生物基因组中的DNA二级结构。G4s 被认为参与多种生物过程。酰基辅酶 A 结合蛋白 (ACBP) 是真核细胞中普遍表达且高度保守的蛋白质，通过转运和保护酰基辅酶 A 酯在脂质代谢中发挥重要作用。在这里，我们报告了家蚕和人类癌细胞中 ACBP 基因启动子中 G4 的功能鉴定。我们发现 G4 作为保守元件存在于无脊椎动物和脊椎动物 ACBP 基因的启动子中。BmACBP G4 与 G4 结合蛋白 LARK 结合调节 BmACBP 转录，该转录被 G4 稳定剂吡哆醇 (PDS) 和 G4 反义寡核苷酸阻断。用五龄家蚕幼虫进行 PDS 处理可降低 BmACBP 表达和甘油三酯 (TAG) 水平，从而导致脂肪体重、体型和体重以及生长和变质率降低。PDS 处理和敲除人肝腺癌 HepG2 细胞中的 HsACBP G4 可抑制 HsACBP 的表达并降低 TAG 水平和细胞增殖。总之，我们的研究结果表明 ACBP 基因的 G4 参与了无脊椎动物和脊椎动物脂质代谢过程的调节。PDS 处理和敲除人肝腺癌 HepG2 细胞中的 HsACBP G4 可抑制 HsACBP 的表达并降低 TAG 水平和细胞增殖。总之，我们的研究结果表明 ACBP 基因的 G4 参与了无脊椎动物和脊椎动物脂质代谢过程的调节。PDS 处理和敲除人肝腺癌 HepG2 细胞中的 HsACBP G4 可抑制 HsACBP 的表达并降低 TAG 水平和细胞增殖。总之，我们的研究结果表明 ACBP 基因的 G4 参与了无脊椎动物和脊椎动物脂质代谢过程的调节。