ノンヒストンScm3とヒストンCenH3-H4は,セントロメア特異的な核細胞の核を構成する
Gaku Mizuguchi1, Hua Xiao, Jan Wisniewski
1Laboratory of Biochemistry and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 6068, Bethesda, MD 20892-4255, USA.
Cell
|June 19, 2007
まとめ
新しいタンパク質であるScm3は,芽生えた酵母におけるヒストンH3変異体Cse4のセンターメリック結合に不可欠である. Scm3は,セントロメアでCse4-H4の組み立てを促進し,カノニカルなH2A-H2Bヒストンを潜在的に置き換えることができます.
科学分野:
- 分子生物学は分子生物学である.
- クロマチンの生物学
- イースト遺伝学 イースト遺伝学
背景:
- セントロメリッククロマチンは,細胞分裂中の正確な染色体分離に不可欠です.
- ヒストンH3変異体Cse4は,キネトコア組立を指揮する,セントロメリックヌクレオソームの重要な構成要素である.
- セントロメアにおけるCse4の組み込みと維持の正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- Cse4と相互作用し,そのセントロメリック局所化に関与するタンパク質を特定する.
- セントロメリッククロマチンの組立と安定性におけるScm3の役割を解明する.
- Scm3,Cse4,およびカノニカルヒストンの構造的および機能的関係を調査する.
主な方法:
- タンパク質の相互作用を検出するために,共免疫プレシピテーションとウエスタン・ブロッティング.
- 細菌の発現と再結合タンパク質の浄化 in vitro 結合アッセイ.
- ヒストン-DNA複合体の再構成.
- セントロメアにおけるヒストンのインビボ占有率の分析.
主要な成果:
- Scm3は,Cse4とコロカライズし,そのセントロメリックアソシエーションに必要な新しい非ヒストンタンパク質として特定されました.
- Scm3はCse4とヒストンH4に直接結合し,安定した複合体を形成するが,従来のH3-H4には結合しない.
- Scm3の保存された酸性ドメインは,Cse4との特定の相互作用を媒介する.
- Scm3結合は,Cse4を含むヒストンオクタマーからヒストンH2A-H2Bを異動させることができる.
- In vivoでは,Scm3はセントロメアにおけるH2A,H2B,H2AZの占有率の低下と相関しています.
結論:
- 非ヒストンタンパク質Scm3は,センターメリック領域におけるCse4-H4複合体の組み立てと維持に不可欠です.
- Scm3は,センターメリック・ヌクレオソーム・コア内のヒストンH2A-H2Bダイマーの代替として機能する可能性があります.
- これらの発見は,バルククロマチンと異なる,セントロメリック核細胞組成と機能のためのユニークなメカニズムを明らかにします.
関連する概念動画
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02:33The 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...
01:19The 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...
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...