通过RAD6介导的转录合的H2B无处不在直接刺激人类细胞中的H3K4甲基化
Jaehoon Kim1, Mohamed Guermah, Robert K McGinty
1The Rockefeller University, New York, NY 10065, USA.
Cell
|May 5, 2009
概括
这项研究确定了人类RAD6作为H2B无处不在的E2酶,这对基因转录至关重要. 它揭示了这个过程如何刺激H3K4甲基化,影响基因表达调节.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因规则 基因规则
背景情况:
- H2B无处不在与活跃转录有关,但其在人体细胞中的机制尚不清楚.
- 此前,hBRE1 已被确定为负责人类细胞中 H2B 无处不在的 E3 酶.
研究的目的:
- 为了在人类细胞中识别H2B无处不在的E2结合酶.
- 在转录过程中阐明H2B无处不在的机制.
- 确定H2B无处不在对转录和基因组修饰的功能后果.
主要方法:
- 同免疫沉以评估蛋白质相互作用.
- 染色体免疫沉 (ChIP) 用于分析蛋白质对基因的招募.
- 西方涂抹用于检测基因素的无处不在和甲基化状态.
主要成果:
- hRAD6被确定为H2B无处不在的E2结合酶.
- hRAD6与hBRE1直接相互作用,并被招募到转录的基因中.
- 在lysine 120的H2B无处不在取决于hPAF介导的转录.
- H2B无处不在刺激了hSET1依赖的H3K4二和三甲基化.
- H2B无处不在不会直接影响hPAF,SII和p300调解的转录水平.
结论:
- 该研究确定了H2B在人体细胞中无处不在的关键因素和机制.
- H2B无处不在作用于转录启动和延伸的下游.
- 这种无处不在的事件在调节下游表观遗传修饰,特别是H3K4甲基化中发挥着关键作用.
相关概念视频
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,...
02:32Histone 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...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
02:38Heterochromatin
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...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.