関連する実験動画
Updated: May 10, 2026
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
ヒストンアセチルトランスフェラーゼ複合体は,プロモーター核分裂体へのSWI/SNF結合を安定させる
A H Hassan1, K E Neely, J L Workman
1Howard Hughes Medical Institute and Department, of Biochemistry and Molecular Biology, The Pennsylvania State University, 16802, University Park, PA, USA
Cell
|April 6, 2001
まとめ
SWI/SNF染色体リモデレータは,転写活性化剤によってプロモーターに誘導され,核分裂を引き起こします. その保持には,HAT複合体によるアクティベーターまたはヒストンのアセチル化が必要です.
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
- クロマチンの生物学
背景:
- SWI/SNFは,重要な染色体改造複合体である.
- 遺伝子プロモーターにおけるその正確な役割を理解することは極めて重要です.
- その採用と維持のメカニズムは完全に解明されていません.
研究 の 目的:
- プロモーターにおけるサイト固有のクロマチンの改造におけるSWI/SNFの機能を調査する.
- SWI/SNFの分布,機能,およびトランスクリプションアクティベーターによるリクルート後の保持を分析する.
- SWI/SNFとヒストンアセチルトランスフェラーゼ (HAT) コンプレックスとの相互作用を解明する.
主な方法:
- 精製されたシステムを生化学分析に使用した.
- 配列特異の転写活性化剤によるSWI/SNFの徴募を研究した.
- プロモーター近接核分裂体における核分裂体破壊とSWI/SNF保持を評価した.
- SAGAおよびNuA4 HAT複合体によるヒストンアセチル化の役割を調査した.
主要な成果:
- アクティベーターの募集により,SWI/SNF結合と局所的な核細胞分裂が発生した.
- SWI/SNFの保持は,継続的なアクティベーター結合またはヒストンアセチル化に依存した.
- SAGAまたはNuA4によるヒストンのアセチル化により,プロモーターのSWI/SNF保持が強化された.
- HATとSWI/SNFの間の機能的なリンクが示されました.
結論:
- SWI/SNFはプロモーターに勧誘され,アクティベーター結合時に核細胞を再構成する.
- HATによるヒストンのアセチル化は,プロモーターにSWI/SNF結合を安定させる.
- これらの発見は,染色体改変複合体の秩序ある徴用のためのメカニズム的基礎を提供します.
関連する概念動画
02:54Nucleosome 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...
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,...
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
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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,...
01:12The Nucleosome Core Particle
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...