Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells
复制标题
DOI：
10.7554/elife.34081
复制
发表时间：
2018-10-02
期刊：
影响因子：
7.7
通讯作者：
Houseley, Jonathan
中科院分区：
文献类型：
--
作者：
Cruz, Cristina;Della Rosa, Monica;Houseley, Jonathan
蛋白质编码基因的转录伴随着COMPASS向启动子近端染色质的募集，其甲基化组蛋白H3赖氨酸4（H3K4）以形成H3K4me1、H3K4me2和H3K4me3。在这里，我们确定了COMPASS在芽殖酵母的整个生命周期中维持基因表达的重要性。我们发现COMPASS突变减少了复制寿命，并导致近500个基因的表达缺陷。虽然H3K4甲基化主要作用于基因阻遏，特别是在酵母中，但阻遏功能随着年龄的增长而逐渐丧失，而数百个基因的完全表达依赖于H3K4me3。这些基因的基础和诱导型表达也在缺乏COMPASS组件Swd1或Spp1的年轻细胞中受损。衰老过程中的基因诱导与启动子H3K4me3的增加有关，但H3K4me3也在非启动子区域和核糖体DNA中积累。我们的研究结果提供了明确的证据表明，H3K4me3是维持许多基因在整个生物体寿命的正常表达所必需的。
Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which methylates histone H3 lysine 4 (H3K4) to form H3K4me1, H3K4me2 and H3K4me3. Here, we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations reduce replicative lifespan and cause expression defects in almost 500 genes. Although H3K4 methylation is reported to act primarily in gene repression, particularly in yeast, repressive functions are progressively lost with age while hundreds of genes become dependent on H3K4me3 for full expression. Basal and inducible expression of these genes is also impaired in young cells lacking COMPASS components Swd1 or Spp1. Gene induction during ageing is associated with increasing promoter H3K4me3, but H3K4me3 also accumulates in non-promoter regions and the ribosomal DNA. Our results provide clear evidence that H3K4me3 is required to maintain normal expression of many genes across organismal lifespan.