HP1のコンフォームスイッチは,ヘテロクロマチンアセンブリを駆動するために自己抑制を放出します
Daniele Canzio1, Maofu Liao, Nariman Naber
1Department of Biochemistry and Biophysics, University of California San Francisco, California 94158, USA.
Nature
|March 15, 2013
まとめ
ヘテロクロマチンタンパク質1 (HP1) は,メチル化核細胞に結合し,Swi6を自己抑制状態から拡散能力のある状態に切り替えますが,これは遺伝子静止とヘテロクロマチンの組立に不可欠です.
科学分野:
- クロマチンの生物学
- エピジェネティクス エピジェネティクス
- 遺伝子調節の分子メカニズム
背景:
- ヒストンH3ライシン9 (H3K9) -メチル化ヘテロクロマチンは,ヘテロクロマチンタンパク質1 (HP1) を含む隣接する領域に広がります.
- HP1はH3K9-メチル化クロマチンを認識し,オリゴメリゼ化し,遺伝子サイレンシングと染色体分離のためのプラットフォームを形成します.
- HP1のメチル化核分裂体への組み立てと,その機能的汎用性は十分に理解されていません.
研究 の 目的:
- HP1タンパク質がメチル化ヌクレオソームのテンプレートに組み立てられる方法を解明する.
- HP1-ニュクレオソーム複合体の機能的汎用性の背後にあるメカニズムを理解する.
- Swi6 (HP1) のメチル化核細胞への結合における自己抑制状態から拡散能力のある状態へのスイッチを調査する.
主な方法:
- スウィ6核細胞複合体の冷凍電子顕微鏡による再構築.
- 自動抑制/拡散に適した状態スイッチを妨害する影響を評価するインビボ試験.
主要な成果:
- Swi6がメチル化核細胞に結合すると,自己抑制状態から拡散能力のある状態への切り替えが起こります.
- 自動抑制状態では,ヒストン模倣配列が染色体メチルマークの認識をブロックする.
- 自己抑制は,H3K9メチルマークと核細胞DNAの両方を認識することで緩和され,拡散のための"粘着性のある端"を暴露します.
- このスイッチの障害は, in vivo ヘテロクロマチンアセンブリと遺伝子サイレンシングを損なう.
結論:
- HP1核群の相互作用には,条件付きの活性化メカニズムがあり,自己抑制と能力の拡散の間で切り替わります.
- このスイッチは,H3K9メチルマークと核細胞DNAの両方の認識によって制御されます.
- この発見は,クロマチンの拡散と遺伝子静止のための新しい規制メカニズムを明らかにしています.
関連する概念動画
02:54Nucleosome Remodeling
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02:25Spreading of Chromatin Modifications
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03:17Inheritance of Chromatin Structures
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
01:01Euchromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
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...