UpSETはHDAC複合体を採用し,プロモーター領域におけるクロマチンのアクセシビリティとアセチル化を制限する
Hector Rincon-Arano1, Jessica Halow, Jeffrey J Delrow
1Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cell
|November 27, 2012
まとめ
この研究は,Drosophilaの転写レギュレータであるupsETを特定し,アクティブクロマチンのマークの拡散を防ぐ. その欠如は,転写ノイズの増加と女性の不妊症につながる.
科学分野:
- エピジェネティクスと遺伝子調節
- 発達生物学 発達生物学について
- クロマチンの生物学
背景:
- 発達の遺伝子発現は,遺伝的および表遺伝的相互作用に依存しています.
- SETドメインのタンパク質は,トランスクリプションのレギュレータとして知られています.
- Rpd3/Sin3複合体はヒストンの脱酸化に関与しています.
研究 の 目的:
- ドロソフィラの新しいSETドメインを含む転写レギュレータであるupSETを特徴付ける.
- クロマチンのアクセシビリティと遺伝子発現におけるupSETの役割を調査する.
- オオゲネシスと女性の生育能力におけるupSETの機能を理解する.
主な方法:
- ドロソフィラのupSET遺伝子とタンパク質の識別と特徴付け.
- 野生型およびupSET変異のハエにおけるクロマチンのアクセシビリティとヒストンのアセチル化パターンの分析.
- 転写ノイズや重複要素の活性化を含む遺伝子発現の評価.
- upSET変異体におけるオオゲネシス中のノッチ信号伝達経路のコンポーネントの検査.
主要な成果:
- UpSETは,Rpd3/Sin3複合体内で機能する,活性遺伝子に採用された転写調節体です.
- UpSETは,プロモーター領域へのクロマチンのアクセシビリティとヒストンのアセチル化を制限する.
- upSETの喪失は,クロマチンのアクセシビリティが増加し,アクティブマークが遺伝子および側面の領域に広がります.
- upSETの欠如は,転写ノイズの増加,重複要素の活性化,および標的外遺伝子発現を引き起こす.
- upSET突然変異のハエは,オオゲネシス中のNotchシグナル伝達コンポーネントのアップレギュレーションにより,雌の不妊性を示す.
結論:
- UpSETは,メタゾーン型転写レギュレータの新種を定義しています.
- UpSETは,活性クロマチンの拡散を制限することによって,微調整トランスクリプションに不可欠です.
- upSET機能の調節不良は,染色体組織,遺伝子発現の忠誠度,および生殖発達に影響を与えます.
関連する概念動画
02:54Nucleosome Remodeling
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Nucleosome remodeling complex
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Nucleosome remodeling complex
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02:32Histone Modification
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Acetylation
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Acetylation
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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
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Writers
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02:38Heterochromatin
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...
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,...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...