遺伝的再結合は,マウスの機能的なゲノム要素から遠ざけられている

Kevin Brick¹, Fatima Smagulova, Pavel Khil

¹National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.

Nature

|June 5, 2012

まとめ

PRDM9タンパク質は,通常,遺伝子の再結合を特定のホットスポットに誘導する. 遺伝子が存在しない場合,再結合は依然として起こりますが,遺伝子プロモーターやその他のゲノム部位に再誘導されます.

科学分野:

遺伝学遺伝学とは
分子生物学は分子生物学である.
生殖生物学生殖生物学

背景:

分離期中の遺伝的再結合は,ゲメトゲネシスと種化にとって極めて重要です.
9を含むPRドメイン (PRDM9) はヒストンメチルトランスフェラーゼで,哺乳類の再結合と特異化に関連しています.
PRDM9の亜鉛指ドメインは,配列特異結合を通じて再結合ホットスポットを指定すると考えられている.

研究の目的:

Prdm9ノックアウトマウスと異なるマウス株における再結合開始部位の全ゲノム分布をマッピングし,分析する.
再結合ホットスポット位置の決定におけるPRDM9の役割を明らかにする.
PRDM9から独立した再結合のメカニズムを理解するために.

主な方法:

再結合開始部位の全ゲノムマッピング.
Prdm9ノックアウトマウス,異なるアレルを持つ野生型のマウス,およびF(1) ハイブリッドにおける再結合パターンの分析.
リコンビネーション部位におけるヒストンの改変,特にH3K4トリメチル化の調査.

主要な成果:

PRDM9は,シュードオートソーマル領域 (PAR) を除き,ほぼすべての哺乳類再結合ホットスポットの位置を決定する.
再結合ホットスポットは,H3K4トリメチル化マークに局限された,Prdm9ノックアウトマウスに存在します.
PRDM9が存在しない場合,再結合は主にプロモーターおよび他のPRDM9独立のH3K4トリメチル化部位で開始されます.

結論:

PRDM9は,マウスのゲノムにおける再結合ホットスポット位置の主な決定因子である.
PRDM9は,遺伝子プロモーターと機能的ゲノム要素の再結合を防止する意外な役割を果たしています.
この研究では,PRDM9が重要な規制領域から遠ざけて再結合を誘導する新しい機能を明らかにした.

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