転写因子結合親近性の分析に基づく哺乳類の強化剤の全ゲノム予測
Outi Hallikas1, Kimmo Palin, Natalia Sinjushina
1Molecular and Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Finland.
Cell
|January 18, 2006
まとめ
研究者は,転写因子結合特異性をマッピングし,遺伝子増強剤を特定するためのツールを開発しました. これは,ヒトの遺伝子発現とその発達と癌における役割の理解を前進させる.
科学分野:
- 分子生物学は分子生物学である.
- ゲノミクスゲノミクスとは
- バイオインフォマティックス
背景:
- 人間の遺伝子発現は,転写因子 (TF) と増強因子によって調節される.
- TF結合の組み合わせコードを理解することは,遺伝子調節の解読に不可欠です.
- Hedgehog (Hh),Wnt,Ras/MAPKのような重要な信号伝達経路には,特定のTFが含まれています.
研究 の 目的:
- GLI1-3,Tcf4,c-Ets1 TFsのDNA結合特性を決定する.
- 哺乳類のエンハンサー要素をゲノムスケールで識別するための計算ツール (エンハンサー要素ロケータ - EEL) を開発する.
- 開発と疾患に関与する標的遺伝子の調節における特定された強化剤の役割を調査する.
主な方法:
- TF DNAの結合特異性を決定するために,新しい高通量法が採用されました.
- 拡張エレメントロケータ (EEL) コンピューティングツールが開発され,利用されました.
- 予測は,変異遺伝子マウス胚を用いて検証された.
主要な成果:
- GLI1-3,Tcf4,c-Ets1のDNA結合特異性が決定されました.
- EELはHhとWntの標的遺伝子を成功裏に特定し,活性化されたTFを予測しました.
- ネズミのc-MycおよびN-Myc遺伝子の組織特異増強剤が特定され,in vivoで検証されました.
結論:
- この研究は,ヒトの遺伝子発現を支配する"第2の遺伝子コード"を明らかにしている.
- 開発されたEELツールは,経路調節強化剤の大規模な識別を可能にします.
- 発見は,腫瘍における臓器特異的成長と腫瘍遺伝子の特異性を理解する上で重要な意味を持つ.
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