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KRYPTONITEヒストンH3メチルトランスフェラーゼによるCpNpGDNAメチル化の制御
James P Jackson1, Anders M Lindroth, Xiaofeng Cao
1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles 90095, USA.
Nature
|March 19, 2002
まとめ
遺伝子サイレンシングは,ヘテロクロマチンの形成を伴う. KRYPTONITE遺伝子は,植物におけるDNAメチル化と遺伝子静止を制御するヒストンメチル化を調節する.
科学分野:
- エピジェネティクスと遺伝子調節
- 植物分子生物学 植物分子生物学
- クロマチンの生物学
背景:
- ユカリオットの遺伝子サイレンシングは,DNAメチル化,ヒストンH3リシン9 (H3 Lys9) メチル化,およびヘテロクロマチンタンパク質1 (HP1) 結合によって特徴づけられるヘテロクロマチン形成に関連しています.
- 特に植物におけるこれらのエピジェネティックマークの間の正確な関係は,ほとんど解明されていないままである.
- Neurospora crassaでは,DNAメチル化はH3 Lys 9メチル化の下流に作用し,保存された規制経路を示唆しています.
研究 の 目的:
- アラビドプシス・タリアナの遺伝子静止とヘテロクロマチン形成の調節に関与する遺伝子を特定する.
- 遺伝子サイレンシングの制御におけるヒストンメチレーションとDNAメチレーションの関係を解明する.
- エピジェネティック・レギュレーションにおける新たに特定されたクリプトナイト遺伝子の機能を特徴づける.
主な方法:
- アラビドプシス・スーパーマン (SUP) ローカスにおける遺伝子静止抑制剤の突然変異スクリーン.
- KRYPTONITEメチルトランスフェラーゼ遺伝子の分離と特徴付け.
- クリプトニット機能喪失変異体におけるDNAメチル化パターン (CpNpG部位) とレトロトランスポーソン活性に関する分析.
- CMT3,HP1の同類体,メチル化ヒストンの間のタンパク質とタンパク質の相互作用を調査する.
主要な成果:
- 新しいH3 Lys 9メチルトランスフェラーゼであるKRYPTONITE遺伝子が特定されました.
- 機能喪失のクリプトニットアレルは,CpNpGDNAメチル化と内生レトロトランスポーソンの再活性化が低下しており,CHROMOMETHYLASE3 (CMT3) の変異体と似ています.
- CMT3は,アラビドプシスのHP1同種と相互作用し,同種はメチル化ヒストンと結合する.
結論:
- CpNpGのDNAメチル化は,ヒストンH3 Lys9メチル化によって表遺伝的に制御されます.
- KRYPTONITE-CMT3-HP1経路は,ヒストンとDNAメチル化信号を統合して,遺伝子静止とゲノム安定性を維持します.
- この研究は,植物における遺伝子静止のためにヒストンのメチル化とDNAメチル化を結びつける保存されたメカニズムを明らかにしています.
関連する概念動画
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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...