基因组H3R2通过PRMT6和H3K4通过MLL复合物的甲基化是相互排斥的
Ernesto Guccione1, Christian Bassi, Fabio Casadio
1Department of Experimental Oncology, European Institute of Oncology (IEO), IFOM-IEO Campus, Milan 20139, Italy.
Nature
|September 28, 2007
概括
基因组甲基化标记,特别是H3R2me2a和H3K4me3,对抗性地调节基因表达. PRMT6酶介导H3R2me2a,该酶从含有H3K4me3.3的活性促进体中耗尽.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 细胞基因组具有 euchromatic 和 heterochromatic 域,通过基因组的翻译后修改 (标记) 来区分.
- 这些标记,特别是在促进体区域,定义了染色体的功能状态,并由复杂的相互作用来调节.
- 之前的研究指出,在人类促进体上,素H3阿尔金因2非对称二甲基化 (H3R2me2a) 和H3素4二甲基化和三甲基化 (H3K4me2,H3K4me3) 之间存在反相关性.
研究的目的:
- 研究PRMT6在催化H3R2二甲基化中的作用.
- 阐明H3R2me2a和H3K4甲基化之间的调控关系.
- 了解哺乳动物基因组中H3R2me2a的分布和调节.
主要方法:
- 在体外酶分析以确定PRMT6对H3R2.2的活性.
- 在体内研究以评估PRMT6对全球H3R2me2a水平的控制.
- 染色体免疫沉 (ChIP) 用于绘制H3R2me2a和H3K4me3在人类基因上的分布图.
主要成果:
- 鉴定出PRMT6是催化H3R2二甲基化在体外的酶,并控制其体内水平.
- 发现H3K4me3阻止了PRMT6的H3R2甲基化,而H3R2me2a抑制了H3K4甲基化和MLL家族复合物的结合.
- H3R2me2a在基因体和3'末端中富含,但选择性地从活跃促进体中耗尽,与H3K4me3的存在一致.
结论:
- 在H3R2和H3K4甲基化之间存在相互对抗的关系.
- 这种对抗性涉及PRMT6和MLL家族复合体,有助于活性哺乳动物促进体的特定H3K4三甲基化模式.
相关概念视频
Spreading 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...
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,...
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...
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...
Chromatin Structure Regulates pre-mRNA Processing
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...
The chromatin structure, especially...
Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.


