染色体改造因子Mll1は,産後神経幹細胞からの神経生成に不可欠です
Daniel A Lim1, Yin-Cheng Huang, Tomek Swigut
1Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Street M779, San Francisco, California 94143, USA. limd@neurosurg.ucsf.edu
Nature
|February 13, 2009
まとめ
混合血統白血病1型 (Mll1) は,成人の神経生成に不可欠である. Mll1は静止された遺伝子の位置を解消し,産後脳におけるニューロン分化を可能にします.
科学分野:
- 神経科学は神経科学である.
- エピジェネティクス エピジェネティクス
- 幹細胞生物学 幹細胞生物学
背景:
- 成人の神経生成は表遺伝的メカニズムに依存し,トリソラックス群 (trxG) とポリコンブ群 (PcG) の遺伝子がクロマチンを調節する.
- PcGメンバーのBmi1が神経幹細胞の自己再生に不可欠であることが知られているが,このプロセスにおけるtrxG遺伝子の役割は未知のものである.
研究 の 目的:
- 産後神経生成におけるtrxG遺伝子Mll1 (混合血統白血病1) の役割を調査する.
- Mll1がサブベントリキュラーゾーンにおけるニューロン分化に影響を与える分子メカニズムを解明する.
主な方法:
- Mll1欠乏症のマウスの分析により,産後脳における神経生成を評価した.
- 神経幹細胞における遺伝子発現分析 (Mash1,Olig2,Dlx2) について.
- MLLの標的を特定するためのクロマチンの免疫プレシピテーション.
- ターゲット遺伝子ロシエットにおけるヒストロン変異分析 (H3K4me3,H3K27me3)
主要な成果:
- Mll1欠乏神経幹細胞は,神経分化が損なわれているが,正常な膠質分化を示す.
- ニューロゲネシスの重要な調節体Dlx2の発現は,Mll1欠乏細胞で廃止されています.
- Dlx2はMLLの直接的な標的であり,そのロクスはMll1欠乏細胞の双価ヒストンマーク (H3K4me3とH3K27me3) を示し,活性化を阻害する.
結論:
- Mll1は,Dlx2.2のような重要な遺伝子の発現を活性化することによって,産後神経生成に不可欠です.
- Mll1は,重要な発達部位における二価クロマチンの痕跡を解消することで機能し,それによって神経細胞の分化を促進します.
- これらの発見は,成人神経生成を調節する新しい表遺伝的メカニズムを強調しています.
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