関連する実験動画
Updated: May 17, 2026
08:56
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S-アデノシルメチオニンとヒストンのメチル化に対するスレオニン代謝の影響
Ng Shyh-Chang1, Jason W Locasale, Costas A Lyssiotis
1Stem Cell Transplantation Program, Division of Pediatric Hematology and Oncology, Manton Center for Orphan Disease Research, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Science (New York, N.Y.)
|November 3, 2012
まとめ
トレオニンは,マウスの胚性幹細胞の多能性にとって不可欠であり,S-アデノシルメチオニン (SAM) の生成を促進します. この代謝リンクはヒストンのメチル化を調節し,幹細胞の成長と分化に影響を与えます.
科学分野:
- バイオケミストリー バイオケミストリー
- 発達生物学 発達生物学について
- 幹細胞生物学 幹細胞生物学
背景:
- トレオニンは,マウス胚性幹細胞 (mESC) の多能性にとって重要なアミノ酸です.
- トレオニンの役割の基礎となる正確な分子機構は,ほとんど不明のままである.
研究 の 目的:
- トレオニンがmESCの多能性をサポートするメカニズムを解明する.
- トレオニンの代謝,S-アデノシルメチオニン (SAM) 合成,および多能幹細胞におけるヒストンのメチル化との関連を調査する.
主な方法:
- メタボリック経路を追跡するためにmESCの同位体ラベルを使用しました.
- mESC培養において,トリオニンまたはトリオニン脱水素酵素 (Tdh) の欠乏.
- 定量化されたS-アデノシルメチオニン (SAM) レベルとヒストンH3ライシン4トリメチル化 (H3K4me3).
主要な成果:
- トレオニンは,SAM合成に必要な細胞グリシンとアセチル-CoAプールに大きく貢献します.
- トレオニン減少またはTdhノックアウトはSAM蓄積とH3K4me3レベルを低下させた.
- 減少したSAMとH3K4me3は,細胞成長の減速と分化の増加と相関していた.
結論:
- トレオニンの代謝は,多能幹細胞のSAM合成と結合し,ヒストンのメチル化を調節する.
- SAMの豊富さは,H3K4me3.3の重要な調節因子であるようです.
- トレオニン代謝のような代謝経路を調節することで,幹細胞の運命に影響を与えることができます.
関連する概念動画
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,...
01:17Phase II Reactions: Methylation Reactions
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
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...
02:41Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...