通过KRYPTONITE 基因组 H3 甲基转移酶控制 CpNpG DNA 的甲基化
James P Jackson1, Anders M Lindroth, Xiaofeng Cao
1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles 90095, USA.
Nature
|March 19, 2002
概括
基因沉默涉及到异染色体的形成. 克里普托尼特基因调节基因组甲基化,控制植物中DNA甲基化和基因沉默.
科学领域:
- 表观遗传学和基因调控
- 植物分子生物学 植物分子生物学
- 染色体生物学 染色体生物学
背景情况:
- 在真核生物中,基因沉默与异性染色质的形成有关,其特点是DNA甲基化,组分素H3氨酸9 (H3 Lys 9) 甲基化和异性染色质蛋白1 (HP1) 结合.
- 这些表观遗传标记之间的确切关系,特别是在植物中,仍然在很大程度上未被阐明.
- 在Neurospora crassa中,DNA甲基化作用于H3 Lys 9甲基化的下游,表明一种保存的调节途径.
研究的目的:
- 为了确定参与调节基因沉默和阿拉比多opsis thaliana中的异色素蛋白形成的基因.
- 为了阐明控制基因沉默中的基因甲基化和DNA甲基化之间的关系.
- 描述新发现的克里普顿基因在表观遗传调节中的功能.
主要方法:
- 在阿拉比多普西斯超人 (SUP) 位点对基因沉默抑制剂的突变屏幕.
- 克里普托尼特甲基转移酶基因的分离和表征.
- 在矿功能丧失突变体中分析DNA甲基化模式 (CpNpG位点) 和逆转移素活性.
- 调查CMT3,HP1同类物和甲基化组织蛋白之间的蛋白质-蛋白质相互作用.
主要成果:
- 鉴定出了KRYPTONITE基因,一种新的H3 Lys 9甲基转移酶.
- 功能丧失的ptonite等位基因表现出减少的CpNpG DNA甲基化和内源逆转移子的重新激活,类似于CHROMOMETHYLASE3 (CMT3) 中的突变.
- CMT3与Arabidopsis HP1同类物相互作用,这反过来又与甲基化组织蛋白结合.
结论:
- CpNpG DNA甲基化是通过基因素H3 Lys 9甲基化进行表观遗传控制的.
- 克里普托尼特-CMT3-HP1通路整合了基因素和DNA甲基化信号,以保持基因沉默和基因组稳定性.
- 这项研究揭示了一种保存的机制,将基因组甲基化与植物基因沉默的DNA甲基化联系起来.
相关概念视频
02:10The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
01:12The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...