希斯H4氨酸16乙化调节细胞寿命
Weiwei Dang1, Kristan K Steffen, Rocco Perry
1Gene Expression and Regulation Program, The Wistar Institute Philadelphia, Pennsylvania 19104, USA.
Nature
|June 12, 2009
概括
酵母细胞随着年龄的增长显示Sir2蛋白减少,导致表观遗传变化和转录沉默的丧失. 这种Sirtuin通路可能被保留来调节衰老并维持端粒染色素.
科学领域:
- 表观遗传学和分子生物学
- 细胞衰老和长寿研究研究
背景情况:
- 表观遗传变化,如DNA甲基化和基因素修饰,驱动细胞发育.
- 赛尔图因是与长寿相关的NAD (((+) 依赖酶,但它们的衰老机制尚不清楚.
- 酵母 Sir2 脱乙化基 H4 素 16 以维持染色体沉默.
研究的目的:
- 研究sirtuins,特别是酵母Sir2在复制性衰老中的作用.
- 阐明酵母菌中与年龄相关的表观遗传变化背后的分子机制.
- 确定Sir2和组织蛋白修饰对寿命调节的贡献.
主要方法:
- 对年轻酵母细胞和复制性老酵母细胞中Sir2蛋白质丰度的分析.
- 评估基因组H4素16的乙化水平和基因组占用在亚端粒区域.
- 研究Sir2和Sas2 (希斯乙转移酶) 在寿命调节中的相互作用.
主要成果:
- 复制老酵母细胞表现出降低的Sir2蛋白水平.
- 在老化的细胞中,H4 lysine 16乙化和基因组损失的增加发生在子端粒区域.
- 在老酵母中观察到在子端粒位置的转录沉默受损.
- Sir2和Sas2的对抗性活动通过H4氨酸16在分端体区域调节寿命.
结论:
- 与年龄相关的Sir2蛋白质的减少导致表观遗传失调和酵母的沉默受损.
- 这种对复制性衰老的Sirtuin介导途径与其他已知的模型不同.
- 赛尔图因可能通过端粒染色体维护在衰老调节中具有进化保守的作用.
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...
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...
02:04Covalently 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.
03:17Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...