通过HMGI(Y) 乙化协调转录开关
N Munshi1, T Agalioti, S Lomvardas
1Department of Biochemistry and Molecular Biophysics, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
概括
干扰素-β (IFN-β) 基因表达的动态控制依赖于增强酶体复合体. 它的组装和拆卸由HMGI(Y) 乙化调节,不同的位点影响稳定性和转录.
科学领域:
- 分子生物学分子生物学
- 基因规则 基因规则
- 免疫学 免疫学 免疫学
背景情况:
- 干扰素-β (IFN-β) 基因表达对抗病毒反应至关重要.
- 增强酶体复杂的组装和拆卸动态调节IFN-β转录.
- 像CBP和PCAF/GCN5这样的基因组乙转移酶 (HAT) 参与增强酶体功能.
研究的目的:
- 研究HMGI(Y) 乙化在IFN-β基因表达的动态控制中的作用.
- 确定HMGI上的特定氨酸残留物如何影响增强酶体稳定性和转录.
- 为了阐明CBP和PCAF/GCN的有序乙化机制5.
主要方法:
- 对内源性促进体活性进行分析.
- 研究高流动性I组 (HMG I(Y)) 蛋白质的乙化.
- 研究CBP和PCAF/GCN5在HMGI(Y) 乙化中的作用.
主要成果:
- 在明确的氨酸残留物 (CBP的K65,PCAF/GCN5的K71) 上对HMGI的有序乙化对于IFN-β转录控制至关重要.
- 在K65的CBP对HMGI (Y) 的乙化破坏了增强酶体的稳定.
- 通过PCAF/GCN5在K71处对HMGI(Y) 的乙化稳定增强酶体并促进转录,防止CBP介导的乙化.
结论:
- 在定义的部位通过特定的HATs对HMGI(Y) 的精确乙化决定了增强酶体稳定性和IFN-β转录.
- 这种有序乙化机制为控制抗病毒反应提供了一个调节开关.
相关概念视频
Covalently 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.
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,...
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...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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,...


