PHF8はヒストンH4ライシン20脱メチル化イベントを媒介し,細胞サイクル進行に関与する
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
まとめ
研究者らはPHF8を,H4K20me1マークを除去するヒストン脱メチラーゼとして特定した. この酵素は細胞サイクル進行に役割を果たし,ヒストンの改変を遺伝子調節とミトーシスと結びつける.
科学分野:
- エピジェネティクス エピジェネティクス
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- 逆戻り可能なヒストンの改変は,様々な生物学的機能を調節する.
- ヒストンH4ライシン20 (H4K20me1) の特異的なデメチラゼとその役割は以前は知られていなかった.
研究 の 目的:
- H4K20me1の脱メチル化に起因する酵素を特定し,特徴づけること.
- 細胞プロセスにおけるH4K20me1脱メチル化の調節作用を解明する.
主な方法:
- PHF8の脱メチラゼ活性を特定するための生化学的分析.
- タンパク質とDNAの相互作用を分析するためのクロマチン免疫プレシピテーションシーケンシング (ChIP-Seq).
- 細胞サイクル進行と遺伝子発現の分析.
主要な成果:
- ジュモンジ・C (JmjC) ドメインを含むタンパク質であるPHF8は,H4K20me1デメチラーゼとして識別され,H3K9me1/2およびH3K27me2.2にも作用しています.
- PHF8は,PHDドメインのH3K4me2/3との相互作用によってプロモーターに勧誘され,H4K20me1.1を除去することによってG1-S移行を調節します.
- プロフェーゼ中のクロマチンからのPHF8のリン酸化依存の放出は,早期ミトーシスにおけるH4K20me1の蓄積に不可欠であり,それをコンデンシンII負荷と結びつける.
結論:
- PHF8は新しいH4K20me1デメチラーゼで,細胞サイクル進行において重要な役割を果たしています.
- この研究は,PHF8によるH4K20me1の脱メチル化と,プロモーターにおける遺伝子調節と,コンデンシンIIを含むミトーシスプロセスとの関連性を明らかにした.
関連する概念動画
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...
02:32Histone 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
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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...