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在素H3R2处的氨酸甲基化控制了H3K4三甲基化沉积的过程
Antonis Kirmizis1, Helena Santos-Rosa, Christopher J Penkett
1Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QN, UK.
Nature
|September 28, 2007
概括
在H3R2的基因组氨酸甲基化通过阻断Spp1的识别来阻止H3K4的三甲基化. 这一发现揭示了一种通过染色体结构修改调节基因表达的新机制.
科学领域:
- 表观遗传学和分子生物学
- 染色体生物学 染色体生物学
- 基因规则 基因规则
背景情况:
- 通过染色质结构来调节生物过程,质子的修饰至关重要.
- 基因组H3 lysine 4三甲基化 (H3K4me3) 与活跃的基因有关.
- 基因组H3氨酸2二甲基化 (H3R2me2a) 的功能和基因组分布在很大程度上是未知的.
研究的目的:
- 研究H3R2me2a在芽酵母 (Saccharomyces cerevisiae) 中的基因组分布和功能.
- 阐明H3R2甲基化和H3K4三甲基化之间的机制关系.
主要方法:
- 在芯片上使用特定的H3R2me2a抗体进行染色体免疫沉降 (ChIP-chip).
- 在整个酵母基因组中分析H3R2me2a分布.
- 生物化学试验评估H3R2甲基化对Set1甲基转移酶对H3K4三甲基化的影响.
主要成果:
- H3R2me2a含有丰富的异性染色素和非活性的 euchromatic 基因,并且在适度转录的基因的 3' 端.
- H3R2me2a模式与H3K4me3.3相互排斥
- 在H3R2的甲基化通过封闭Spp1子单元,阻止Set1复合体对H3K4的三甲基化.
结论:
- 甲基化H3R2通过抑制H3K4三甲基化作为抑制标记.
- 该机制涉及Spp1亚单元的固体阻碍,防止Set1介导的H3K4三甲基化.
- 这项研究提供了对氨酸甲基化在染色质调节中的作用的第一个机制性见解.
相关概念视频
Histone 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
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Acetylation
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Writers
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Writers
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Histone Variants at the Centromere
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
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Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
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Histone 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,...

