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Unique patterns of trimethylation of histone H3 lysine 4 are prone to changes during aging in Caenorhabditis elegans somatic cells

机译:组图H3赖氨酸4的三甲基化的独特模式在秀丽隐杆线虫体细胞的衰老过程中易于改变

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摘要

Tri-methylation on histone H3 lysine 4 (H3K4me3) is associated with active gene expression but its regulatory role in transcriptional activation is unclear. Here we used Caenorhabditis elegans to investigate the connection between H3K4me3 and gene expression regulation during aging. We uncovered around 30% of H3K4me3 enriched regions to show significant and reproducible changes with age. We further showed that these age-dynamic H3K4me3 regions largely mark gene-bodies and are acquired during adult stages. We found that these adult-specific age-dynamic H3K4me3 regions are correlated with gene expression changes with age. In contrast, H3K4me3 marking established during developmental stages remained largely stable with age, even when the H3K4me3 associated genes exhibited RNA expression changes during aging. Importantly, the genes associated with changes in H3K4me3 and RNA levels with age are enriched for functional groups commonly implicated in aging biology. Therefore, our findings suggested divergent roles of H3K4me3 in gene expression regulation during aging, with important implications on aging-dependent pathophysiologies.
机译:组蛋白H3赖氨酸4(H3K4me3)上的三甲基化与活跃的基因表达有关,但其在转录激活中的调控作用尚不清楚。在这里,我们使用秀丽隐杆线虫研究H3K4me3和衰老过程中基因表达调控之间的联系。我们发现了大约30%的H3K4me3富集区域显示出随年龄的显着且可复制的变化。我们进一步显示,这些年龄动态H3K4me3区在很大程度上标记了基因体,并在成年阶段获得。我们发现,这些成年特定的年龄动态H3K4me3区与基因表达随年龄的变化相关。相反,即使H3K4me3相关基因在衰老过程中表现出RNA表达变化,在发育阶段建立的H3K4me3标记也会随着年龄的增长而保持稳定。重要的是,与H3K4me3和RNA水平随年龄的变化相关的基因富含衰老生物学中通常涉及的功能基团。因此,我们的研究结果表明H3K4me3在衰老过程中基因表达调控中的作用不同,这对衰老相关的病理生理学具有重要意义。

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