eRNAによって機能的に定義された異なる種類の強化剤によってトランスクリプションを再プログラムする.
Dong Wang1, Ivan Garcia-Bassets, Chris Benner
1Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0651, USA.
Nature
|May 17, 2011
まとめ
FoxA1のような細胞系因子は,アンドロゲン受容体 (AR) を制御し,強化剤に結合する. FoxA1のダウンレギュレーションは,ARを新しい強化剤にシフトさせ,前立腺がんの進行に影響を与えることによって,ホルモン反応を再プログラムします.
科学分野:
- ゲノミクスゲノミクスとは
- 分子生物学は分子生物学である.
- 癌生物学 癌生物学について
背景:
- 哺乳類のゲノムには,細胞型特異的な遺伝子発現に不可欠な何千もの転写強化剤が含まれています.
- 増強剤が信号依存の転写反応を媒介するメカニズムは完全に理解されていません.
研究 の 目的:
- 細胞系因子がアンドロゲン受容体 (AR) のような調節された転写因子の活性にどのように影響するか調査する.
- 増強剤へのAR結合を調節するFoxA1の役割とその前立腺がんへの影響を調査する.
主な方法:
- 増強剤の活性とRNAの生成を分析するために,グローバル核ランオンシーケンシング (GRO-seq).
- FoxA1レベルに対する反応におけるアンドロゲン受容体 (AR) 結合ダイナミクスの分析.
主要な成果:
- FoxA1などの細胞系因子は,特異な増強剤クラスへの転写因子の結合を促進したり制限したりすることができます.
- 前立腺腫瘍における予後不良のマーカーであるFoxA1のダウンレギュレーションは,異なる強化剤のセットにAR結合の有意なシフトを引き起こします.
- 機能増強剤が増強剤テンプレート型非コーディングRNA (eRNA) を生成し,一部のクラスが核細胞リモデリングなしに遺伝子発現を活性化する証拠.
- 結合されたARは,転写開始と延長の両方を誘導するようです.
結論:
- 活性増強剤の豊富な貯蔵庫が存在し,ダイナミックに調節され,代替遺伝子発現プログラムを生成することができます.
- これらの発見は,特に前立腺がんにおいて,発育,分化,および疾患進行における連続的な遺伝子発現イベントの洞察を提供します.
- AR増強剤の関与を調節するFoxA1の役割は,進行した前立腺腫瘍における潜在的な治療的脆弱性を強調しています.
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