マウスゲノムの空間的組織と,再発する染色体転位におけるその役割
Yu Zhang1, Rachel Patton McCord, Yu-Jui Ho
1Howard Hughes Medical Institute, Children's Hospital Boston and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Cell
|February 21, 2012
まとめ
ゲノムの3D組織は,染色体転位,特にDNA二重鎖断裂 (DSB) の近くに大きな影響を与えます. ゲノム位置だけでなく,空間的近接が,がんゲノミクスにおける転位形成を促しています.
科学分野:
- ゲノミクスゲノミクスとは
- 癌生物学 癌生物学について
- 分子生物学は分子生物学である.
背景:
- 3次元 (3D) のゲノム組織は,細胞機能にとって極めて重要です.
- 染色体転位は多くの癌の特徴であり,DNAの二重鎖断裂 (DSB) から生じる可能性があります.
- ゲノム構造とトランスロケーション形成の相互作用を理解することは,がんゲノミクスにおける鍵です.
研究 の 目的:
- 染色体転位形成に3Dゲノム組織の貢献を調査する.
- マウスのプロB細胞ゲノムの高解像度の空間図の中で,DSBに関連したトランスロケーションをマッピングする.
- トランスロケーションを推進する空間的近接の役割を明らかにする.
主な方法:
- G1で逮捕されたマウスプロB細胞ゲノムの高解像度のHi-C空間組織マップを生成しました.
- ターゲットDSBから発生するトランスロケーションをマッピングするために,高通量ゲノム全体のトランスロケーションシーケンシングを使用しました.
- 空間的近接効果を直接評価するために電離放射線を用いた標準化されたDSB.
主要な成果:
- RAGエンドヌクレアゼで割れた抗原受容体ロシは,ターゲットDSBの支配的な転位パートナーとして特定されました.
- トランスロケーションは,単一の染色体に沿ったcisで,および既存の空間的近接に基づいて他の染色体内で有意に濃縮されました.
- この研究では,空間的近接と転位の濃縮の間の直接的な関係が示されました.
結論:
- 3Dゲノム組織は,染色体転位を指揮する上で重要な役割を果たします.
- DNA二重鎖の断裂の空間的近接は,ゲノム位置とは関係なく,転位形成の主要な決定因子です.
- この研究は,統合型ゲノム学的方法を用いてがんのゲノム変異に関する新しい視点を提供します.
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