転写因子ファミリーのDNA特異性の進化により,新しい遺伝子調節モジュールが生まれた
Alesia N McKeown1, Jamie T Bridgham1, Dave W Anderson1
1Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA.
Cell
|September 27, 2014
まとめ
転写因子DNA結合特異性の進化は,ステロイドホルモン受容体で研究されました. 重要な突然変異は,祖先のDNA結合を弱め,同時に新しい配列の認識を可能にし,特異性の進化の負の決定因子を明らかにしました.
科学分野:
- 分子生物学は分子生物学である.
- 進化生物学の進化生物学について
- バイオケミストリー バイオケミストリー
背景:
- 転写因子 (TF) は,特定のDNA配列を結合することによって,遺伝子ネットワークを調節する.
- TFDNAの結合特異性の進化を理解することは,遺伝子調節を解読する上で極めて重要です.
- ステロイドホルモン受容体 (SR) 家族は,TF進化を研究するためのモデルを提供します.
研究 の 目的:
- ステロイドホルモン受容体 (SR) 家族の中でDNA認識がどのように多様化したか調査する.
- 新型TFDNA結合特異性の進化の基礎となる分子メカニズムを解明する.
主な方法:
- 進化の歴史を追跡するための系統遺伝分析.
- DNA結合の親和性と特異性を測定するための生化学的測定法.
- TFsとDNAの間の分子相互作用を調査するための生体物理学技術.
主要な成果:
- SR遺伝子コピーの3つの特定の突然変異は,祖先のエストロゲン応答要素 (ERE) に結合を弱めた.
- これらの変異は同時に,新しいステロイド反応要素 (SREs) に結合を強めた.
- 負の決定因子 (不利な相互作用) と許容的置換は,変化したDNAの選択性および結合親和性に決定的であった.
結論:
- DNA結合の負の決定因子は,TF配列の選択性において重要な役割を果たします.
- 新型TFDNA結合特異性の進化は,先祖の規制モジュールを破壊することなく起こる可能性があります.
- この研究は,TFDNA結合とリガンド特異性の共進化のメカニズムを明らかにしています.
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