通过雌激醇和lncRNAHOTAIR动态调节BDNF基因表达
Paromita Deb1, Avisankar Chini1, Prarthana Guha1
1Gene Regulation and Epigenetics Research Lab, Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019, United States.
Gene
|December 3, 2023
概括
雌激醇 (E2) 通过取代抑制因素,促进神经元中的脑衍生神经变因子 (BDNF) 基因表达. 这项研究揭示了E2.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 大脑衍生神经营养因子 (BDNF) 对神经元健康至关重要,其失调与神经退行性疾病有关.
- 雌激素 (E2) 是一种关键激素,影响神经元分化和可塑性,特别是在海马体.
研究的目的:
- 研究基底条件下BDNF基因表达的调节机制以及对雌激醇 (E2) 的反应.
- 阐明E2如何调节神经元细胞中的BDNF表达.
主要方法:
- 染色体免疫沉 (ChIP) 试验用于评估BDNF促进体的蛋白质丰富.
- 使用HT22细胞的体外研究和在卵巢切除小鼠体内研究.
- 对于HOTAIR knockdown 的RNA干扰 (RNAi).
主要成果:
- 在细胞培养和小鼠大脑中,E2治疗增加了BDNF表达.
- 雌激素受体 (ERα,ERβ) 在E2刺激时与BDNF促进体结合,同时增加了基因素乙化和活性转录机制.
- 长非编码RNAHOTAIR,与PRC2和LSD1一起,在基底条件下抑制BDNF表达;HOTAIR敲击缓解了这种抑制.
结论:
- 通过促进沉默复合体 (EZH2,LSD1) 的位移,并将活性转录因子招募到BDNF促进剂,E2诱导BDNF表达.
- 霍泰尔通过调节促进体组素修饰来作为BDNF基因表达的抑制剂.
- 这些发现揭示了神经元中E2和HOTAIR对BDNF基因调节的关键分子机制.
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