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酵母和小鼠中组蛋白修饰对新生DNA甲基化的体内靶向作用。

In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse.

作者信息

Morselli Marco, Pastor William A, Montanini Barbara, Nee Kevin, Ferrari Roberto, Fu Kai, Bonora Giancarlo, Rubbi Liudmilla, Clark Amander T, Ottonello Simone, Jacobsen Steven E, Pellegrini Matteo

机构信息

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.

Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy.

出版信息

Elife. 2015 Apr 7;4:e06205. doi: 10.7554/eLife.06205.

DOI:10.7554/eLife.06205
PMID:25848745
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4412109/
Abstract

Methylation of cytosines (5(me)C) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 shows an increase of relative 5(me)C levels at the transcription start site and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methylation in vivo.

摘要

胞嘧啶甲基化（5(me)C）是一种广泛存在的可遗传DNA修饰。在哺乳动物发育过程中，两次全基因组去甲基化事件之后是多轮DNA从头甲基化。DNA甲基化建立的体内机制在很大程度上尚未明确。在此，我们以缺乏DNA甲基化的酿酒酵母作为系统，来确定影响小鼠DNMT3B活性的染色质特征。我们的数据表明，DNMT3B与H3K4甲基化相互排斥，且DNMT3B与H3K36甲基化区域共定位。为支持这一观察结果，对缺乏Set1和Set2的酵母菌株进行的DNA甲基化分析显示，转录起始位点的相对5(me)C水平升高，而基因体中的相对5(me)C水平降低。我们将这一观察结果扩展到小鼠雄性生殖系，其中H3K4me3呈强烈负相关，而H3K36me3与加速的DNA甲基化相关。这些结果表明H3K36甲基化对体内基因体DNA甲基化的重要性。

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