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DNA甲基化的基因组模式:一种表观遗传标记的靶点与功能

Genomic patterns of DNA methylation: targets and function of an epigenetic mark.

作者信息

Weber Michael, Schübeler Dirk

机构信息

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.

出版信息

Curr Opin Cell Biol. 2007 Jun;19(3):273-80. doi: 10.1016/j.ceb.2007.04.011. Epub 2007 Apr 26.

Abstract

Methylation of cytosines can mediate epigenetic gene silencing and is the only known DNA modification in eukaryotes. Recent efforts to map DNA methylation across mammalian genomes revealed limited DNA methylation at regulatory regions but widespread methylation in intergenic regions and repeats. This is consistent with the idea that hypermethylation is the default epigenetic state and serves in maintaining genome integrity. DNA methylation patterns at regulatory regions are generally stable, but a minor subset of regulatory regions show variable DNA methylation between cell types, suggesting an additional dynamic component. Such promoter de novo methylation might be involved in the maintenance rather than the initiation of silencing of defined genes during development. How frequently such dynamic methylation occurs, its biological relevance and the pathways involved deserve investigation.

摘要

胞嘧啶甲基化可介导表观遗传基因沉默,是真核生物中唯一已知的DNA修饰。近期绘制哺乳动物全基因组DNA甲基化图谱的研究发现,调控区域的DNA甲基化有限,但基因间区域和重复序列中存在广泛的甲基化。这与高甲基化是默认表观遗传状态并有助于维持基因组完整性的观点一致。调控区域的DNA甲基化模式通常是稳定的,但一小部分调控区域在不同细胞类型之间显示出可变的DNA甲基化,这表明存在额外的动态成分。这种启动子从头甲基化可能参与了发育过程中特定基因沉默的维持而非起始。这种动态甲基化发生的频率、其生物学相关性以及涉及的途径值得研究。

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