PHF8调解了参与细胞循环进展的素H4氨酸20脱甲基化事件
Wen Liu1, Bogdan Tanasa, Oksana V Tyurina
1Howard Hughes Medical Institute, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Nature
|July 13, 2010
概括
研究人员确定PHF8是一种消除H4K20me1标记的基因组脱甲基酶. 这种酶在细胞循环进展中发挥作用,将基因素修饰与基因调节和线粒分裂联系起来.
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
- 细胞生物学 细胞生物学
背景情况:
- 可逆转基因组修饰调节各种生物功能.
- 具体的甲基酶对 histone H4 lysine 20 (H4K20me1) 和它们的作用以前是未知的.
研究的目的:
- 为了识别和描述负责H4K20me1脱甲基化的酶.
- 阐明H4K20me1脱甲基化在细胞过程中的调节作用.
主要方法:
- 生物化学测试以确定PHF8的脱甲基酶活性.
- 染色体免疫沉测序 (ChIP-Seq) 用于分析蛋白质-DNA相互作用.
- 细胞周期进展和基因表达的分析.
主要成果:
- PHF8,一个含有Jumonji C (JmjC) 域的蛋白质,被确定为H4K20me1脱甲基酶,也对H3K9me1/2和H3K27me2.2起作用.
- PHF8通过其PHD域与H3K4me2/3的相互作用被招募到促进器中,并通过去除H4K20me1.1来调节G1-S过渡.
- 在预相过程中,PHF8从染色质中依赖酸化的排放对H4K20me1在早期线粒分裂中的积累至关重要,将其与凝聚酶II负载联系起来.
结论:
- PHF8是一种新的H4K20me1脱甲基酶,在细胞循环进展中起着关键作用.
- 这项研究揭示了PHF8通过H4K20me1脱甲基化和促进体的基因调节以及涉及凝聚素II的线粒体过程之间的联系.
相关概念视频
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.
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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,...
00:50Anaphase Promoting Complex
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01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...