对Ad4BP/SF-1的DNA甲基化抑制了Cyp11a1和C2C12核细胞中的Star转录
Jumpei Fujiki1, Naoyuki Maeda2, Kosuke Yamaguchi1
1Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
Molecular and cellular endocrinology
|August 2, 2024
概括
基因甲基化调节C2C12核细胞中的类固醇生成. 脱甲基化Ad4BP/SF-1可以调节类固醇基因Cyp11a1和StAR,影响皮质的生物合成.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 类固醇生成发生在外围组织和内分泌腺体中.
- 鼠标的C2C12神经细胞和老鼠的骨肌肉具有局部的葡萄糖皮质激素通路.
- 这些组织中缺少关键的类固醇基因表达 (Cyp11a1,StAR).
研究的目的:
- 研究DNA甲基化在调节类固醇基因中的作用.
- 检查Ad4BP/SF-1甲基化与类固醇基因表达之间的关系.
- 确定脱甲基化对C2C12核细胞中的类固醇生成的影响.
主要方法:
- 甲基化DNA免疫沉的生物信息学分析.
- 用5-aza-2-deoxycytidine (一种去甲基化剂) 治疗C2C12细胞核细胞.
- 通过敲击抑制Ad4BP/SF-1基因沉默.
- 基因表达的量化 (Ad4BP/SF-1,Cyp11a1,StAR) 和孕的水平.
主要成果:
- Cyp11a1基因体没有显著的DNA甲基化,但Ad4BP/SF-1内基增强剂具有甲基化CpG岛.
- 5-aza-2-deoxycytidine治疗以时间和剂量依赖的方式上调Ad4BP/SF-1,Cyp11a1和Star基因表达.
- 即使在去甲基化处理后,Ad4BP/SF-1敲击抑制了Cyp11a1和StAR表达和孕隆的产生.
结论:
- 对Ad4BP/SF-1的DNA甲基化可能会降低C2C12核细胞中的类固醇基因 (Cyp11a1,StAR) 的下调.
- 在这个模型中,Ad4BP/SF-1是Cyp11a1和STAR表达的关键转录因子.
- 通过DNA甲基化的表观遗传调节在局部类固醇生成中起着重要作用.
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