統合された空間ゲノミクスは,単一の核のグローバルアーキテクチャを明らかにする
Yodai Takei1, Jina Yun1, Shiwei Zheng2,3
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Nature
|January 28, 2021
まとめ
研究者達は,何千もの染色体位置,核構造,単一のマウス細胞の遺伝子発現をマッピングしました. 彼らは核の組織に固定された点を発見し 遺伝性クロマチンの痕跡を特定し 細胞状態の洞察を明らかにしました
科学分野:
- 細胞生物学
- ゲノミクス
- エピジェネティクス
背景:
- 染色体構造,核組織,遺伝子発現の関係を理解することは極めて重要です.
- 個々の細胞の高度な多様性は,同じ細胞内の複数のモダリティをマッピングすることを必要とします.
研究 の 目的:
- マウスの胚性幹細胞の染色体位置,染色質状態,核体,RNA発現を空間的にマッピングする.
- 核組織における固定点を特定し,染色体マークと遺伝子発現との関連を明らかにする.
- クロマチンマークの遺伝性を調査し,異なる細胞亜集団を特定する.
主な方法:
- 単一のマウス胚性幹細胞 (ES) の3,660の染色体位置をイメージするためにDNAseqFISH+を使用した.
- 17の染色体マークと亜核構造をマッピングするために 連続免疫光を用いた.
- 同じ細胞内の70のRNAの発現プロフィールを評価した.
主要な成果:
- 特定の免疫光マークと常に関連付けられている"固定点"として多数のロキスを特定しました.
- 遺伝子発現の爆発に関係なく,高度に発現した遺伝子が活性な核圏に先行位置づけられていることが観察されました.
- 特定の組み合わせクロマチンの状態を特徴とする異なるマウスのES細胞亜集団を発見した.
- 特定の染色体マーク (H3K27me3,mH2A1) は3〜4世代に渡って受け継がれ,他のものは急速に変動することを示した.
結論:
- seqFISH+ベースの空間的マルチモダルのアプローチは,核組織と細胞状態を探求するための強力なツールを提供します.
- 固定された点と遺伝子の先行位置づけは,遺伝子発現に影響を与える構造化された核組織を示唆する.
- 染色体マークの遺伝性は,細胞の同一性と変化性を維持する表遺伝的メカニズムを強調する.
さらに関連する動画
関連する概念動画
The Nucleosome
DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
Nucleosome 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...
DNA Microarrays
Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...
The Nucleosome
DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
The Nucleosome
Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
The 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...


