ヒストンのアセチル化と転写の調節は,オンコタンパク質のセットを含むヒト細胞複合体であるINHATによって行われます
1Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Cell
|February 13, 2001
まとめ
新しい細胞複合体であるアセチルトランスフェラーゼ阻害剤 (INHAT) はヒストンのアセチル化と転写制御を阻害する. この複合体はヒストンを結合し,アセチルトランスフェラーゼ酵素からマスクして,新しい調節機構を提供する.
科学分野:
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
- 遺伝子規制 遺伝子規制
背景:
- p300/CBPやPCAFのような酵素によるヒストンのアセチル化が遺伝子転写に不可欠である.
- ヒストンのアセチル化と転写を調節する細胞機構は,まだ完全に理解されていません.
研究 の 目的:
- ヒストンアセチルトランスファーゼ (HAT) 活性を調節する細胞因子を特定し,特徴づけること.
- 細胞活動が転写を制御するメカニズムを解明する.
主な方法:
- 多タンパク質細胞複合体の浄化と特徴付け.
- 複合体内の新しいアセチルトランスファーゼ阻害ドメインのマッピング.
- クロマチンのインビボ関連研究.
- トランスクリプションの調節を評価するために,トランスクリプションされた細胞での機能分析.
主要な成果:
- アセチルトランスフェラーゼ阻害剤 (INHAT) と呼ばれる多タンパク質複合体は,p300/CBPとPCAF HATの活性を強力に抑制するものであることが確認された.
- INHAT内の新しい阻害ドメインがマッピングされ,ヒストンと結合し,そのアセチル化を防ぐことができました.
- Set/TAF-Ibetaオンコタンパク質を含む内生INHATサブユニットは,体内ではクロマチンに局所化します.
- 細胞内のINHAT発現は,コアクティベーター媒介の転写をブロックする.
結論:
- INHATはヒストンアセチルトランスフェラーゼの新型阻害剤として機能します.
- INHATによるヒストンマスクは,クロマチンの改変を調節する新しいメカニズムを表しています.
- このヒストンマスクメカニズムは,転写の調節に重要な役割を果たします.
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
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02:25Spreading of Chromatin Modifications
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Writers
The writer is an enzyme that can...
Writers
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01:01Euchromatin
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...
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...
02:38Heterochromatin
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,...