抑圧性ヒストンマークの伝播におけるポリコンブタンパク質EEDの役割
Raphael Margueron1, Neil Justin, Katsuhito Ohno
1Howard Hughes Medical Institute and Department of Biochemistry, New York University Medical School, 522 First Avenue, New York, New York 10016, USA.
Nature
|September 22, 2009
まとめ
ポリコンブ抑制複合体2 (PRC2) のEEDタンパク質は,抑制ヒストンのマークに結合し,その遺伝子静止活性を活性化します. このメカニズムは,クロマチンの状態を維持し,細胞分裂中に表遺伝子情報を伝達するのに役立ちます.
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.
- 発達生物学 発達生物学とは
背景:
- ポリコンブ群のタンパク質は,抑圧的な染色体状態を維持する.
- ポリコンブ抑制複合体2 (PRC2) は,ヒストンH3ライシン27トリメチル化 (H3K27me3) を通して遺伝子静止を媒介する.
- EZH2,SUZ12,EEDはPRC2.2の主要なサブユニットである.
研究 の 目的:
- PRC2の活動におけるEEDサブユニットの役割を調査する.
- PRC2が抑圧的な染色体マークを認識し,拡散するメカニズムを解明する.
主な方法:
- EEDとヒストンの尾の相互作用を研究するための生化学分析.
- PRC2.2の実験室内メチルトランスファーゼ活性測定法
- 発達の影響を評価するために,ドロソフィラのEEDの遺伝子操作.
主要な成果:
- EEDのカルボキシ末端ドメインは,ヒストンの尾のトリメチル化ライシン残留物と結合する.
- この結合は,PRC2.2のメチルトランスファーゼ活性をアロステリックに活性化する.
- トリメチル・ライシン結合を阻害するEEDの変異はPRC2の活性化を廃止し,ドロソフィラの発達障害を引き起こす.
結論:
- EEDは,抑圧的なクロマチンマークのセンサーとして働き,PRC2.2を活性化します.
- このメカニズムは,H3K27me3 マークの増殖と維持に不可欠です.
- この発見は,細胞分裂中に表遺伝的記憶伝達のためのモデルを提案しています.
関連する概念動画
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...
Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
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...
Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
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...


