氨酸代谢对S-adenosylmethionine和基因素甲基化的影响
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.
概括
氨酸对于小鼠胚胎干细胞多能性至关重要,促进S-adenosylmethionine (SAM) 的产生. 这种代谢环节调节了组织素甲基化,影响了干细胞的生长和分化.
科学领域:
- 生物化学 生物化学
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
背景情况:
- 氨酸是小鼠胚胎干细胞 (mESC) 多能性的关键氨基酸.
- 在氨酸的作用背后的精确分子机制仍然在很大程度上是未知的.
研究的目的:
- 阐明氨酸支持mESC多能性的机制.
- 为了研究氨酸代谢,S-adenosylmethionine (SAM) 合成和多能干细胞中的基因组甲基化之间的联系.
主要方法:
- 在mESC中利用同位素标记来追踪代谢途径.
- 在mESC培养物中减弱了氨酸或氨酸脱酶 (Tdh).
- 量化S-adenosylmethionine (SAM) 度和组织素H3氨酸4三甲基化 (H3K4me3).
主要成果:
- 氨酸对SAM合成所需的细胞甘氨酸和乙-CoA池有显著的贡献.
- 氨酸耗尽或Tdh淘汰会降低SAM积累和H3K4me3水平.
- 减少SAM和H3K4me3与细胞生长放缓和分化增加相关.
结论:
- 氨酸的新陈代谢与多能干细胞中的SAM合成相结合,调节组织甲基化.
- 萨姆的丰度似乎是H3K4me3.3的关键调节者.
- 调节代谢途径,如三氨酸代谢,可以影响干细胞的命运.
相关概念视频
Histone 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,...
Histone 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,...
Phase 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...
Spreading 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...
Chromatin 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...
Epigenetic 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...


