低氧诱导了基质子甲基化的快速变化,并重新编程了染色体
Michael Batie1,2, Julianty Frost1, Mark Frost1
1Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK.
概括
低氧迅速增加了独立于HIF的基因组甲基化. 抑制像KDM5A这样的JmjC- 基因组脱甲基酶,模仿低氧,揭示色素
科学领域:
- 生物化学
- 分子生物学
- 表观遗传学
背景情况:
- 氧气对于多细胞生命至关重要,像分子二氧化酶这样的酶利用它.
- 含有 Jumanji-C (JmjC) 域的基脱甲酶是一种二氧化酶的子类.
- 低氧对染色体的影响已知,但JmjC- 基因组脱甲基酶的直接作用尚不清楚.
研究的目的:
- 调查低氧对JmjC-甲基酶的直接影响.
- 为了确定缺氧是否直接改变基因组甲基化.
- 通过染色体探测氧气的机制.
主要方法:
- 使用的人类培养细胞暴露在低氧条件下.
- 监测 histone 甲基化,特别是 histone-3 lysine-4 三甲基化 (H3K4me3) 和 H3K36me3.
- 不激活含有JmjC的酶氨酸脱甲基酶5A (KDM5A),以观察细胞反应.
主要成果:
- 低氧会诱导快速的,低氧诱导的独立于因子的组织蛋白甲基化.
- 特定的基因组甲基化标记 (H3K4me3,H3K36me3) 可以预测后续的转录变化.
- KDM5A的失活有效地模仿了低氧诱导的细胞反应.
结论:
- 染色体通过抑制JmjC- 甲基酶直接感知氧气水平.
- 对于对低毒性条件的反应来说,JmjC- 基因组脱甲基酶活性至关重要.
- 这项研究揭示了细胞中氧气感应的新型表观遗传机制.
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