线粒体TCA循环酶的核定位作为哺乳动物细胞基因组激活的关键步骤
Raghavendra Nagaraj1, Mark S Sharpley1, Fangtao Chi1
1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell
|January 14, 2017
概括
线粒体三碳酸 (TCA) 循环酶在胚胎发育初期暂时进入细胞核,对于表观遗传重塑和胚胎基因组激活至关重要. 酸盐的可用性调节了这种核定位,影响了胚胎的发育.
科学领域:
- 胚胎学
- 表观遗传学
- 代谢调节
背景情况:
- 表观遗传修饰对于转录控制和胚胎发育至关重要.
- 在2细胞阶段的小鼠胚胎中,囊性基因组激活 (ZGA) 涉及全球表观遗传变化.
- 尽管线粒体活性较低,但酸盐对于后2细胞阶段的发育至关重要.
研究的目的:
- 研究线粒体三碳酸 (TCA) 循环代谢物和酶在早期胚胎表观遗传改造中的作用.
- 确定TCA循环酶的核定位对于细胞基因组激活 (ZGA) 的必要性.
主要方法:
- 在小鼠胚胎早期发育过程中分析线粒体酶局部化.
- 与酶核进入相关的基因组修饰和ZGA的评估.
- 研究酸盐在促进TCA循环酶的核定位方面的作用.
主要成果:
- 在早期小鼠胚胎中,酶性活跃的TCA循环酶是暂时且部分局部化的.
- 这些酶的核定位依赖于酸盐,对表观遗传改造和ZGA至关重要.
- TCA循环酶的核进入失败导致组织蛋白修饰的丧失和ZGA的阻断.
- 这些酶在晚期发育阶段仅限于线粒体.
- 在人类胚胎基因组激活过程中,人类酸盐脱酶显示过渡性核定位.
结论:
- 线粒体TCA循环酶在早期哺乳动物植入前发育过程中,在调节表观遗传修饰和ZGA方面发挥着保守的,短暂的核作用.
- 酸盐的可用性是核酶功能的关键代谢调节剂,对于成功的胚胎基因组激活至关重要.
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