ステロイドホルモン受容体の協同結合は,ターゲットの強化要素における転写のシナジズムに寄与する
S Y Tsai1, M J Tsai, B W O'Malley
1Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Cell
|May 5, 1989
まとめ
2つのステロイドホルモン受容体分子はDNAに協力して結合し,遺伝子の活性化を促進します. この協力的結合は,プロゲステロン受容体を著しく増加させます.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- エンドクリノロジー エンドクリノロジー
背景:
- ステロイドホルモン受容体は,ホルモン反応要素 (HREs) と呼ばれる特定のDNA配列に結合することによって,遺伝子発現を調節する.
- 以前は,2つのステロイドホルモン受容体分子が,チロシンアミノトランスフェラゼ遺伝子内の1つのHRE (GRE/PRE) に結合することが示されていた.
研究 の 目的:
- ステロイドホルモンによる遺伝子誘導性に対する複数のHREsの影響を調査する.
- プロゲステロンによるシナギスティック遺伝子誘導の基礎となるメカニズムを決定する.
主な方法:
- 2つのGRE/PREサイトを組み合わせたレポーター遺伝子 (TK-CAT) の構築.
- ゲノム発現を測定するためのプロゲステロン誘導アッセイ.
- 受容体-HREの相互作用を評価するためのDNA結合研究.
主要な成果:
- 2つのタンドームのGRE/PREsは,TK-CAT遺伝子に相乗的なプロゲステロン誘導性を授与しました.
- 結合試験では,第1のサイトを占有すると,第2のGRE/PREサイトに対する受容体結合親和性が100倍増加することが示されました.
- これは,プロゲステロン受容体二分子の協力的結合を示唆しています.
結論:
- ステロイドホルモン受容体と隣接するHREsの協同結合は,相乗的な遺伝子活性化につながる可能性があります.
- このメカニズムは,ホルモン媒介の遺伝子調節の感度と特異性を高めるための分子基盤を提供します.
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