The effects of early-life growth hormone intervention on tissue specific histone H3 modifications in long-lived Ames dwarf mice.
The effects of early-life growth hormone intervention on tissue specific histone H3 modifications in long-lived Ames dwarf mice.
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DOI：
10.18632/aging.202451
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发表时间：
2020-12-28
期刊：
影响因子：
--
通讯作者：
Sun LY
中科院分区：
文献类型：
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作者：
Zhang F;Icyuz M;Bartke A;Sun LY
组蛋白修饰，特别是组蛋白 H3 的赖氨酸残基的修饰，与多种模型生物体的寿命调节有关。我们之前的研究表明，生命早期的生长激素（GH）治疗可以显着影响长寿艾姆斯侏儒小鼠的寿命。然而，这种激素干预对表观遗传修饰的影响从未被研究过。在这项研究中，我们试图比较 Ames 侏儒小鼠和野生型 (WT) 小鼠的组织特异性组蛋白 H3 赖氨酸甲基化和乙酰化标记，并确定这些标记如何受到生命早期 GH 干预的影响。艾姆斯侏儒小鼠的肝和脑组织中的 H3K4me 均受到抑制，而大脑中的 H3K27me 则升高。生命早期的 GH 干预显着改变了这些组织中的组蛋白 H3 标记。此外，早期 GH 干预以组织特异性方式增加了多个赖氨酸残基上组蛋白 H3 乙酰化的表达。这包括肝脏和大脑中的 H3K14ac 和 H3K18ac、内脏脂肪组织中的 H3K18ac 以及皮下脂肪组织中的 H3K9ac、H3K14ac 和 H3K27ac 的变化。这项研究是阐明表观遗传机制的第一步，也是重要的一步，生命早期的激素信号通过该机制影响哺乳动物的衰老和寿命。
Histone modifications, specifically in the lysine residues of histone H3, have been implicated in lifespan regulation in several model organisms. Our previous studies showed that growth hormone (GH) treatment during early life can dramatically influence lifespan in long-lived Ames dwarf mice. However, the effects of this hormonal intervention on epigenetic modifications have never been examined. In this study, we sought to compare tissue-specific histone H3 lysine methylation and acetylation markers in Ames dwarf and wild type (WT) mice and to determine how these markers are affected by early-life GH intervention. Ames dwarf mice exhibited suppressed H3K4me in both hepatic and brain tissues, while showing elevated H3K27me in the brain. Early-life GH intervention significantly altered the histone H3 markers in those tissues. Furthermore, early GH intervention increased expression of histone H3 acetylation at multiple lysine residues in a tissue-specific manner. This included changes in H3K14ac and H3K18ac in the liver and brain, H3K18ac in visceral adipose tissue and H3K9ac, H3K14ac and H3K27ac in subcutaneous adipose tissue. This study serves as an initial, but important step in elucidating the epigenetic mechanisms by which hormonal signals during early life can influence aging and longevity in mammals.