DNA配列に依存する区画化と,核ラミナにおけるクロマチンの静音化
Joseph M Zullo1, Ignacio A Demarco, Roger Piqué-Regi
1Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
Cell
|June 26, 2012
まとめ
ラミナ関連ドメイン (LAD) と呼ばれる不活性染色体ドメインは,遺伝子調節の鍵です. この研究は,特定のDNA配列とLADを確立するタンパク質を特定し,ゲノム組織と遺伝子サイレンシングを結びつける.
科学分野:
- ゲノミクスゲノミクスとは
- エピジェネティクス エピジェネティクス
- 細胞生物学 細胞生物学
背景:
- 哺乳類のゲノムの大部分は,核の周辺に位置する,ラミナ関連ドメイン (LADs) と呼ばれる不活性染色体領域に存在する.
- LADの形成と維持を制御する正確なメカニズムは完全に理解されていません.
研究 の 目的:
- ラミナ関連ドメイン (LAD) の形成の基礎となる分子メカニズムを解明する.
- 核膜とクロマチンの関連と遺伝子抑制に責任を負うDNA配列とタンパク質因子を特定する.
主な方法:
- ゲノム再定位アッセイは,IgHとCyp3aロシオのLADを研究するために使用されました.
- 微細スケールマッピングにより,ラミナ関連配列 (LAS) と関連するモチーフが特定されました.
- タンパク質のノックダウン実験 (cKrox,HDAC3) を実施し,LAD形成におけるそれらの役割を評価した.
主要な成果:
- LADs内の分離されたDNA領域は,クロマチンを核ラミナに固定し,遺伝子活動を抑制することが判明しました.
- ラミナ関連は,ミトーシス中に確立され,アナフェーズの遅い段階でラミンBの徴募を含む.
- ラミナ関連配列 (LAS) は,cKrox,HDAC3,およびLap2βによって結合されたGAGAモチーフのために強化されています.
- cKroxまたはHDAC3のノックダウンにより,LADsの核ラミナとの関連が破壊されました.
結論:
- 新しいメカニズムが明らかにされ,クロマチンのドメインの核区画化と遺伝子の活性調節を結びつける.
- cKrox複合体によって結合されたLAS内のGAGAモチーフは,ラミナ結合と遺伝子抑制を誘導するために重要である.
関連する概念動画
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Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
DNA Packaging
Overview
Chromatin Packaging
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
Chromatin Packaging
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
Chromatin Packaging
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
Heterochromatin
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...


