甲状腺ホルモン受容体は,甲状腺ホルモンとエストロゲン反応要素の共通の配列モチーフに逆の転写効果で結合する
C K Glass1, J M Holloway, O V Devary
1Eukaryotic Regulatory Biology Program, School of Medicine, University of California, San Diego, La Jolla 92093-0613.
Cell
|July 29, 1988
まとめ
甲状腺ホルモン (T3) 受容体は特定のDNA配列を結合し,転写を活性化します. しかし,エストロゲン反応要素を活性化せずに結合し,エストロゲンを抑制します.
科学分野:
- 分子生物学は分子生物学である.
- エンドクリノロジー エンドクリノロジー
- 遺伝学 遺伝学とは
背景:
- 甲状腺ホルモン (T3) 受容体は遺伝子発現を調節する.
- エストロゲン反応要素 (ERE) は,エストロゲン受容体に結合するDNA配列である.
- T3受容体の転写活性化のための正確なDNA結合要件は完全に理解されていません.
研究 の 目的:
- T3受容体のDNA結合特異性を調査する.
- エストロゲン反応要素に結合するT3受容体の機能的影響を決定する.
- T3受容体がEREと相互作用するメカニズムを解明する.
主な方法:
- in vitro DNA結合を評価するための電泳運動シフトアッセイ (EMSA)
- レポーター遺伝子システムを用いたインビヴォ転写活性化アッセイ.
- 中央のパリンドロームモチーフのバリエーションを持つDNA配列の分析.
主要な成果:
- T3受容体は,パリンドロミックなコアモチーフ (5オミノ-TCAGGTCA.TGACCTGA-3オミノ) と中央の"ギャップ"を持つDNA配列に結合する.
- T3受容体は,ERE (ギャップがない) に高 afinity in vitroで結合する.
- T3受容体は,EREsからの転写をin vivoで活性化できず,エストロゲン媒介のトランスアクティベーションを阻害する.
結論:
- T3受容体のDNA結合要素のサブセットだけがT3応答要素として機能する.
- EREsに結合するT3受容体は,転写的に不活性であり,エストロゲン受容体結合と競合する.
- この競争は,エストロゲンに依存した遺伝子発現の純減少につながります.
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