ヒストンH3K9の段階的なメチル化により,核の周辺にヘテロクロマチンが位置する
Benjamin D Towbin1, Cristina González-Aguilera, Ragna Sack
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Cell
|September 4, 2012
まとめ
S-アデノシルメチオニン合成酵素を減らし,C. elegans. のヘテロクロマチンを放出する. このプロセスには,MET-2とSET-25ヒストンメチルトランスフェラーゼが関与し,H3K9メチル化を確立し,ヘテロクロマチンを核周辺に固定します.
科学分野:
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
- エピジェネティクス エピジェネティクス
背景:
- 転写的に抑制されたヘテロクロマチンを核周辺に固定するメカニズムはよく理解されていません.
- ヘテロクロマチンの局所化は,ゲノムの安定性を維持し,遺伝子発現を調節するために重要である.
研究 の 目的:
- ヘテロクロマチンの核結合に関与する要因を特定する.
- ヘテロクロマチン局所化におけるS-アデノシルメチオニン合成酵素と特定のヒストンメチルトランスファーゼの役割を明らかにする.
主な方法:
- Caenorhabditis elegansの胚における全ゲノムRNA干渉 (RNAi) スクリーン.
- MET-2とSET-25を含むヒストンメチルトランスファーゼ (HMTs) の分析.
- ヘテロクロマティックトランスゲンの評価とネイティブ染色体腕の局所化.
主要な成果:
- S-アデノシルメチオニン (SAM) 合成酵素の枯渇は,全体的にヒストンのメチル化を減少させ,核周辺からヘテロクロマチンを放出します.
- MET-2およびSET-25 HMTsのフェノコピーの喪失,SAM合成酵素の枯渇,ヘテロクロマチンの結合を妨害する.
- MET-2とSET-25は連続してH3K9をメチル化し,SET-25はH3K9me3を貯蔵し,周核焦点を形成する.
結論:
- SAM合成酵素とHMTsのMET-2とSET-25は,C. elegans.の核周辺にヘテロクロマチンを固定するのに不可欠です.
- 連続したHMT経路であるMET-2にSET-25が続くと,ヘテロクロマチン局所化にとって重要なH3K9メチル化が確立される.
- SET-25は,その産物に依存する自己強化の環核局所化を示しており,ヘテロクロマチン伝播のメカニズムを示唆しています.
関連する概念動画
Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
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...
Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Chromatin Position Affects Gene Expression
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...


