Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York City, United States of America.
Computational Biology Service Unit, Cornell University, Ithaca, New York City, United States of America.
PLoS Genet. 2018 Jun 18;14(6):e1007466. doi: 10.1371/journal.pgen.1007466. eCollection 2018 Jun.
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.
组蛋白 H3 赖氨酸 4 三甲基化（H3K4me3）与基因的活跃表达有关，但它在转录激活中的调控作用尚不清楚。在这里，我们利用秀丽隐杆线虫来研究在衰老过程中 H3K4me3 与基因表达调控之间的联系。我们发现大约 30%的 H3K4me3 富集区域随着年龄的增长而发生显著且可重复的变化。我们进一步表明，这些与年龄相关的 H3K4me3 区域主要标记基因的外显子，并且是在成年阶段获得的。我们发现这些成年特异性的与年龄相关的 H3K4me3 区域与基因表达随年龄的变化相关。相比之下，在发育阶段建立的 H3K4me3 标记在很大程度上随着年龄的增长保持稳定，即使 H3K4me3 相关基因在衰老过程中表现出 RNA 表达的变化。重要的是，与 H3K4me3 和 RNA 水平随年龄变化相关的基因富集了与衰老生物学密切相关的功能组。因此，我们的研究结果表明 H3K4me3 在衰老过程中的基因表达调控中发挥了不同的作用，这对与衰老相关的病理生理学具有重要意义。
