胰岛素受体与基因组范围内的促进体关联并调节基因表达
Melissa L Hancock1, Rebecca C Meyer1, Meeta Mistry2
1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|April 9, 2019
概括
胰岛素受体 (IR) 进入细胞核,调节代谢和糖尿病等疾病中的基因. 这一发现揭示了胰岛素的新途径
科学领域:
- 分子生物学
- 代谢调节
- 基因组学
背景情况:
- 胰岛素受体 (IR) 信号对代谢控制至关重要,但其长期影响尚未完全理解.
- 红外信号的失调与糖尿病,神经退化和癌症等慢性疾病有关.
研究的目的:
- 阐明胰岛素信号的长期影响背后的机制.
- 研究胰岛素受体的核功能及其在基因调节中的作用.
主要方法:
- 全基因组染色体免疫沉 (ChIP) 以确定红外结合位点.
- 对胰岛素反应的基因表达变化的分析.
- 通过共免疫沉和西式涂抹来研究蛋白质与蛋白质的相互作用.
主要成果:
- 发现胰岛素受体 (IR) 与RNA聚合酶II结合,并与全基因组的基因促进体结合.
- 由IR调节的目标基因参与脂质代谢,蛋白质合成以及包括糖尿病和癌症在内的疾病.
- 红外染色体结合由胰岛素水平调节,受宿主细胞因子-1 (HCF-1) 的介导而导致胰岛素抵抗受损.
结论:
- 胰岛素受体 (IR) 在核内调节基因转录中发挥直接作用.
- 一个新的HCF-1依赖途径调解胰岛素的转录效应,将细胞表面信号与长期基因表达变化联系起来.
- 这确定了胰岛素作用的新分子机制,与代谢健康和疾病发病有关.
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