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ヒトゲノムにおけるヌクレオソームの位置づけのダイナミックな調節
Dustin E Schones1, Kairong Cui, Suresh Cuddapah
1Laboratory of Molecular Immunology, The National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
Cell
|March 11, 2008
まとめ
人間のT細胞における全ゲノムにわたる核細胞マッピングは,転写のダイナミックな調節を明らかにする. 核粒子の位置はRNAポリメラーゼII結合と相関し,遺伝子の活性化と静止時の変化と相関する.
科学分野:
- エピジェネティクスと遺伝子調節
- 分子生物学は分子生物学である.
- ヒューマンゲノミクス (ヒトゲノミクス)
背景:
- 核子の位置づけは,遺伝子転写の調節に極めて重要です.
- これまでのヒトでの核細胞マッピング研究は,特定のゲノム領域に限られていた.
研究 の 目的:
- 人間のCD4+T細胞における核細胞位置の包括的な全ゲノムマップを作成する.
- 細胞の活性化と遺伝子発現の変化の間に,ニュクレオソームの景観のダイナミックな調節を調査する.
主な方法:
- 核細胞末端の直接シーケンシングは,Solexaの高通量シーケンシング技術を使用して行われます.
- トランスクリプション開始部位に対する核細胞相化の分析.
- 休息中の核細胞組織と活性化されたT細胞の比較.
主要な成果:
- 核細胞相化は,RNAポリメラーゼII結合と直接相関しています.
- アクティブ対サイレント遺伝子の転写開始部位の下流の最初の核細胞で観察された異なる核細胞位置づけ.
- T細胞受容体シグナリングは,プロモーターとエンハンスターにおける広範囲の核細胞の再編成を誘発する.
- 証拠は,H2A.Zを含む,修正された核細胞が -1 位置から優先的に失われることを示唆しています.
結論:
- ヒトゲノムの中核細胞の全貌を包括的に描写しています.
- 細胞シグナル伝達と転写状態への反応として,ニュクレオソームの位置づけのダイナミックな調節を示しています.
- 遺伝子の活性化と抑制を制御するニュクレオソームの再編成の役割を強調しています.
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...
02:35Chromatin Position Affects Gene Expression
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
02:05Duplication of Chromatin Structure
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
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,...
02:32Histone 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...