ATPに依存した核細胞複合体によるクロマチンの脱酸化
J K Tong1, C A Hassig, G R Schnitzler
1Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature
|November 6, 1998
まとめ
研究者らは,ヒト細胞で新しい核細胞再構成および脱セチル化 (NRD) 複合体を発見した. この複合体はヒストン脱酸化酵素とATPに依存した核細胞の再編成活動を結びつけ,遺伝子転写とクロマチンの構造に影響を与えます.
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:
- DNA複製と遺伝子転写を含むエウカリオット染色体ダイナミクスは,核細胞核の組み立てと改造に依存しています.
- ヒストンアセチル化とATP依存型核細胞再構成は,転写を調節する重要な酵素プロセスである.
- ヒストン脱エチラゼ (HDACs) は,オリゴヌクレオソームヒストンの脱エチル化に制限がある in vitro.
研究 の 目的:
- ヒトヒストン脱エチラゼ複合体内の新規のATP依存型核細胞リモデリング活動を特定し,特徴づけること.
- 異なるクロマチンの修飾作用の潜在的結合を調査する.
主な方法:
- ATPに依存した核細胞リモデリング活動を特定し,特徴付けるための生化学的分析.
- ヒストンデセチラゼ複合体の機能分析.
- オリゴヌクレオソームヒストンを用いたインビトロ脱酸化アッセイ.
主要な成果:
- ヒト内生ヒストン脱セチラゼ複合体内の新しいATP依存型核細胞リモデリング活動の特定.
- この活動は,ヘリカーゼ/ATPーゼドメインを有するCHD3およびCHD4タンパク質に起因する.
- 特定された複合体は,ヌクレオソーム再構成および脱セチル化 (NRD) 複合体と呼ばれ,オリゴヌクレオソームヒストンの in vitro 脱セチル化を促進します.
結論:
- ヒストン脱酸化酵素と核細胞の再構築活動との物理的,機能的な関係を確立します.
- NRD複合体は,異なる染色体修飾機能を統合しています.
- 転写とクロマチンの構造の調節に関する新しい洞察を提供します.
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...
02:32Histone 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...
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...