AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans
AMPK blocks starvation-inducible transgenerational defects in Caenorhabditis elegans
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DOI：
10.1073/pnas.1616171114
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发表时间：
2017-03-28
影响因子：
11.1
通讯作者：
Roy, Richard
中科院分区：
文献类型：
--
作者：
Demoinet, Emilie;Li, Shaolin;Roy, Richard
生活史事件，例如创伤性应激、疾病或饥饿，可以通过以特征染色质修饰模式记录的分子变化影响我们。这些修饰通常与基因表达的适应性调整有关，这种调整可以在生物体的整个生命周期中持续存在，甚至跨越多代。尽管这些适应可能会带来一些选择性优势，但如果它们没有得到适当的调节，它们也可能以依赖于环境的方式出现适应不良。我们在此表明，在秀丽隐杆线虫幼虫急性饥饿期间，主要代谢调节因子 AMP 激活蛋白激酶 (AMPK) 在阻止染色质景观的改变中发挥着关键作用。这确保了基因表达在不利条件下在种系前体中保持不活跃。如果没有它，关键的染色质修饰会发生在饥饿的 L1 幼虫的原始生殖细胞 (PGC) 中，这与经历过压力的一代以及从未经历过初始事件的后代的生殖适应性受损相关。我们的研究结果表明，AMPK 调节染色质修饰 COMPASS 复合体（与 Set1 相关的复合蛋白）的活性，以确保在营养/能量意外情况得到满足之前染色质标记不会建立。我们的研究提供了分子见解，将代谢适应与针对急性饥饿期的跨代表观遗传修饰联系起来。
Life history events, such as traumatic stress, illness, or starvation, can influence us through molecular changes that are recorded in a pattern of characteristic chromatin modifications. These modifications are often associated with adaptive adjustments in gene expression that can persist throughout the lifetime of the organism, or even span multiple generations. Although these adaptations may confer some selective advantage, if they are not appropriately regulated they can also bemaladaptive in a context-dependent manner. We show here that during periods of acute starvation in Caenorhabditis elegans larvae, the master metabolic regulator AMP-activated protein kinase (AMPK) plays a critical role in blocking modifications to the chromatin landscape. This ensures that gene expression remains inactive in the germ-line precursors during adverse conditions. In its absence, critical chromatin modifications occur in the primordial germ cells (PGCs) of emergent starved L1 larvae that correlate with compromised reproductive fitness of the generation that experienced the stress, but also in the subsequent generations that never experienced the initial event. Our findings suggest that AMPK regulates the activity of the chromatin modifying COMPASS complex (complex proteins associated with Set1) to ensure that chromatin marks are not established until nutrient/energy contingencies are satisfied. Our study provides molecular insight that links metabolic adaptation to transgenerational epigenetic modification in response to acute periods of starvation.