リンシン9メチルヒストンH3尾に結合したHP1染色体の構造
Steven A Jacobs1, Sepideh Khorasanizadeh
1Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA 22908-0733, USA.
Science (New York, N.Y.)
|February 23, 2002
まとめ
HP1染色体は,ヒストンH3尾をリシン9でメチル化させ,エピジェネティックサイレンシングに不可欠である. 構造分析は,ベータ鎖の挿入と芳香的相互作用を含むこの相互作用が結合親和性にどのように影響するかを明らかにします.
科学分野:
- 構造生物学 構造生物学とは
- エピジェネティクス エピジェネティクス
- タンパク質とDNAの相互作用
背景:
- HP1 (ヘテロクロマチンタンパク質1) タンパク質ファミリーは,表遺伝子の遺伝子調節において重要な役割を果たします.
- HP1染色体は,ヒストンの尾,特にH3K9me.でメチル化されたリジン残基に結合することが知られている.
- この相互作用は,遺伝子の静止に関連したクロマチンの凝縮された形態であるヘテロクロマチンの確立と維持に不可欠です.
研究 の 目的:
- ドロソフィラのHP1染色体とヒストンのH3尾をリジン9 (H3K9me) でメチル化した相互作用の構造的およびエネルギー的基礎を解明する.
- H3K9の異なるメチル化状態 (二対三メチル化) が結合親和性と分子認識にどのように影響するかを理解する.
主な方法:
- 複合体の高解像度構造を決定するX線結晶学.
- 結合のエネルギー分析のための同熱定位熱計 (ITC)
- サイト・ディレクテッド・ミュータゲネシスで,特定の残留物の結合への寄与を調査する.
主要な成果:
- ヒストンH3の尾はベータ鎖形状を採用し,HP1染色体のベータサンドイッチ構造を完了する.
- H3K9meのメチラモニウムグループは,染色体の3つのアロマティックサイドチェーンによって形成されたケージの中に正確に配置されています.
- 隣接する残基とクロモドメインの一面の間の特定の接触が選択的認識を媒介する.
- H3K9 (H3K9me3) のトリメチル化により,二メチル化 (H3K9me2) に比べて結合親和性がわずかに改善され,カチオン-ピとヴァン・デル・ワールスの相互作用の役割を示唆した.
結論:
- この研究は,HP1染色体によるH3K9meの認識のための詳細な分子機構を提供します.
- この発見は,エピジェネティックサイレンシングを媒介する特定の構造的およびエネルギー特性の重要性を強調しています.
- H3K9me2とH3K9me3の結合 afinityの微妙な差異は,ヘテロクロマチン形成の微妙な調節メカニズムを示唆しています.
さらに関連する動画
24:02The ChroP Approach Combines ChIP and Mass Spectrometry to Dissect Locus-specific Proteomic Landscapes of Chromatin
Published on: April 11, 2014
10:09Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
関連する概念動画
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...
02:10The 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.
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
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...