腺病毒小e1a改变了全球基因素修饰模式
Gregory A Horwitz1, Kangling Zhang, Matthew A McBrian
1Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
Science (New York, N.Y.)
|August 23, 2008
概括
腺病毒e1a蛋白与细胞循环的进展联系在一起,通过降低基因素H3 lysine 18乙化 (H3K18ac). 这一发现表明H3K18低乙化在癌症发展中的作用.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 亚地诺病毒e1a蛋白通过与RB蛋白和基因素乙烯转移酶p300/CBP相互作用,诱导细胞循环的进展.
- 通过e1a与p300/CBP结合促进细胞循环进展的确切机制仍然不完全理解.
研究的目的:
- 阐明e1a与p300和CBP相互作用在促进细胞循环通过中的作用.
- 调查e1a对基因组乙化的影响,特别是在基因组H3 lysine 18 (H3K18) 中.
主要方法:
- 研究了腺病毒e1a蛋白,RB家族蛋白质和基因素乙烯转移酶p300/CBP之间的相互作用.
- 量化全球素H3氨酸18乙化 (H3K18ac) 的水平.
- 利用CBP和p300的淘汰来评估它们在H3K18ac.中的作用.
- 在表达SV40 T抗原的细胞和前列腺癌组织中检查H3K18ac水平.
主要成果:
- 与p300/CBP的e1a相互作用导致全球H3K18ac.减少了三倍.
- Knockdown 的 CBP 和 p300 特别导致 H3K18 低乙化,证实了它们在 H3K18 乙化中的作用.
- SV40 T抗原也诱导了H3K18的低乙化.
- 在前列腺癌中观察到全球H3K18低乙化,与预后不佳有关.
结论:
- 腺病毒e1a蛋白通过减少H3K18乙化,至少部分地促进细胞循环的进展.
- 全球H3K18低乙化是一种与瘤转化相关的潜在机制,可以作为侵袭性癌症的生物标志物.
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,...
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...
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...
02:54Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
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...