マルチタンパク質複合体によるc-fos血清応答要素のインビボの占有は,成長因子誘導によって変化しない
R E Herrera1, P E Shaw, A Nordheim
1Zentrum für Molekulare Biologie Heidelberg, Universität Heidelberg, FRG.
Nature
|July 6, 1989
まとめ
c-fos遺伝子は,c-fos遺伝子と呼ばれるものです.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- 細胞シグナル伝達 細胞信号伝達
背景:
- 外部信号によるヒトc-fosプロトオンコゲンの急速な誘導は,血清応答要素 (SRE) に依存する.
- 2つのタンパク質,血清応答因子 (p67SRF) とp62は,SREに結合する.
- これらのタンパク質とSREの相互作用は,c-fos遺伝子誘導に極めて重要です.
研究 の 目的:
- ディメチル硫酸塩のゲノム足跡を用いて,c-fos SREにおけるインビボタンパク質相互作用を調査する.
- ヒトA431細胞におけるSREとその付近領域内のタンパク質とDNAの接触を決定する.
- これらの相互作用が遺伝子の活性化と抑制の間にどのように変化するのかを理解するために.
主な方法:
- ディメチル硫酸塩のゲノム足跡は,タンパク質結合部位をマッピングするために使用されました.
- 人間のA431細胞におけるc-fos SREと隣接する配列のタンパク質-DNA接触の分析.
- エピデルマ・成長因子 (EGF) 誘導の前,中,および後のタンパク質-DNA接触の比較.
主要な成果:
- ゲノム足跡調査は,p67SRF,p62,およびp67SRFへの追加のタンパク質3'と一致する保護と超反応性のパターンを明らかにしました.
- 観察されたSRE内のタンパク質-DNA接触は,EGF誘導前に存在していました.
- これらのコンタクトは,遺伝子の活性化およびその後の抑制を通じて変化しませんでした.
結論:
- c-fos SREには,遺伝子の転写状態に関係なく,安定したDNA-タンパク質構造が存在する.
- SREにおけるこの事前に確立された構造は,細胞外信号に対する迅速な転写反応を促進する一般的な役割を果たす可能性があります.
- この発見は,保存されたタンパク質-DNA相互作用を通じて遺伝子の反応性を維持するメカニズムを示唆しています.
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