Epigenome Mapping in Quiescent Cells Reveals a Key Role for H3K4me3 in Regulation of RNA Polymerase II Activity.

IF 2.5 Q3 GENETICS & HEREDITY
Shengyuan Zeng, Karl Ekwall
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引用次数: 0

Abstract

(1) Background: Quiescent cells are those that have stopped dividing and show strongly reduced levels of gene expression during dormancy. In response to appropriate signals, the cells can wake up and start growing again. Many histone modifications are regulated in quiescence, but their exact functions remain to be determined. (2) Methods: Here, we map the different histone modifications, H3K4me3, H3K9ac, H3K9me2, and H3K9me3, and the histone variant H2A.Z, comparing vegetative and quiescent fission yeast (S. pombe) cells. We also map histone H3 as a control and RNA polymerase II (phosphorylated at S2 and S5) to enable comparisons of their occupancies within genes. We use ChIP-seq methodology and several different bioinformatics tools. (3) Results: The histone modification mapping data show that H3K4me3 changes stand out as being the most significant. Changes in occupancy of histone variant H2A.Z were also significant, consistent with earlier studies. Regarding gene expression changes in quiescence, we found that changes in mRNA levels were associated with changes in occupancy of RNA polymerase II (S2 and S5). Analysis of quiescence genes showed that increased H3K4me3 levels and RNA polymerase II occupancy were super-significant in a small set of core quiescence genes that are continuously upregulated during dormancy. We demonstrate that several of these genes were require Set1C/COMPASS activity for their strong induction during quiescence. (4) Conclusions: Our results imply that regulation of gene expression in quiescent cells involves epigenome changes with a key role for H3K4me3 in regulation of RNA polymerase II activity, and that different gene activation mechanisms control early and core quiescence genes. Thus, our data give further insights into important epigenome changes in quiescence using fission yeast as an experimental model.

静息细胞表观基因组图谱揭示 H3K4me3 在调节 RNA 聚合酶 II 活性中的关键作用
(1) 背景:休眠细胞是指那些停止分裂的细胞,在休眠期间基因表达水平严重下降。在适当信号的作用下,细胞可以唤醒并重新开始生长。许多组蛋白修饰在休眠期受到调控,但它们的确切功能仍有待确定。(2)方法:在这里,我们绘制了不同的组蛋白修饰H3K4me3、H3K9ac、H3K9me2和H3K9me3以及组蛋白变体H2A.Z的图谱,并对无性繁殖和休眠的裂殖酵母(S. pombe)细胞进行了比较。我们还绘制了作为对照的组蛋白 H3 和 RNA 聚合酶 II(在 S2 和 S5 处磷酸化)的图谱,以比较它们在基因中的占位情况。我们使用了 ChIP-seq 方法和几种不同的生物信息学工具。(3)结果:组蛋白修饰图谱数据显示,H3K4me3 的变化最为显著。组蛋白变体 H2A.Z 的占位变化也很明显,这与之前的研究一致。关于静止期基因表达的变化,我们发现 mRNA 水平的变化与 RNA 聚合酶 II 占有率的变化有关(S2 和 S5)。对休眠基因的分析表明,在休眠期持续上调的一小部分核心休眠基因中,H3K4me3水平和RNA聚合酶II占据率的增加是超级显著的。我们证明,这些基因中有几个需要 Set1C/COMPASS 的活性才能在休眠期被强烈诱导。(4) 结论:我们的研究结果表明,静止期细胞中基因表达的调控涉及表观基因组的变化,H3K4me3 在 RNA 聚合酶 II 活性调控中起着关键作用,不同的基因激活机制控制着早期和核心静止期基因。因此,我们的数据进一步揭示了以裂殖酵母为实验模型的静止期表观基因组的重要变化。
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来源期刊
Epigenomes
Epigenomes GENETICS & HEREDITY-
CiteScore
3.80
自引率
0.00%
发文量
38
审稿时长
11 weeks
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