通过间歇性缺氧来增加H3K27乙化,这取决于活性氧物种的增加,由H3S28酸化调节
bioRxiv : the preprint server for biology
|September 24, 2024
概括
间歇性缺氧 (IH) 增加了通过活性氧物种 (ROS) 的基因组3乙化和基因组乙转移酶 (HAT) 和基因组脱乙酶 (HDAC) 之间的相互作用,影响基因表达.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 睡眠医学 睡眠医学
背景情况:
- 基因组蛋白对通过后翻译修饰 (PTMs) 进行基因调节至关重要.
- 间歇性缺氧 (IH),在睡眠呼吸暂停中很常见,与3基因组3乙化 (H3Kac) 和甲基化 (H3Kme) 有关.
- IH诱导的H3乙化的精确分子机制尚不清楚.
研究的目的:
- 为了阐明驱动IH诱导H3乙化的分子机制.
- 研究反应性氧物种 (ROS),基因素乙转移酶 (HAT) 和基因素脱乙酶 (HDAC) 在这个过程中的作用.
- 探索H3乙化和酸化之间的相互作用,以响应IH.
主要方法:
- 使用抗氧化剂和ROS模仿剂来评估ROS参与.
- 作为HDAC抑制剂的Trichostatin A (TSA) 和CTK7A用于抑制p300/CBP (HATs) 的使用.
- 使用酸酶抑制剂,研究了特定的基因组修饰,包括H3K27乙化和H3S28酸化.
主要成果:
- 由IH诱导的H3乙化被抗氧化剂阻断,并被ROS模仿,在这个过程中涉及ROS.
- HDAC抑制模仿了IH诱导的H3乙化,而HAT抑制取消了它,突出了HAT/HDAC相互作用.
- IH特异性乙化H3K27,与H3S28脱化相关;抑制脱化阻断了H3K27乙化,反之亦然.
结论:
- 依赖ROS的HAT/HDAC相互作用调节IH诱导的H3乙化.
- 在对IH的反应中,H3乙化 (H3K27) 和酸化 (H3S28) 之间的平衡至关重要.
- 这些发现揭示了在IH条件下控制基因表达的复杂表观遗传机制.
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