グルココルチコイド受容体:生体細胞の調節部位との急速な交換

J G McNally¹, W G Müller, D Walker

¹Laboratory of Receptor Biology and Gene Expression, Building 41, Room B602, National Cancer Institute, Bethesda, MD 20892-5055, USA.

Science (New York, N.Y.)

|February 26, 2000

まとめ

ステロイド受容体は,生きている細胞のDNA反応要素とダイナミックに相互作用する. ホルモン占有受容体は,クロマチンと核プラズマの間で急速に交換し,より活発な遺伝子調節プロセスを明らかにします.

科学分野:

分子生物学は分子生物学である.
細胞生物学細胞生物学
遺伝学遺伝学とは

背景:

ステロイド受容体は遺伝子発現の重要な調節体であり,ホルモン依存の細胞反応を媒介する.
これらの受容体は,染色体内の応答要素として知られる特定のDNA配列に結合します.
これらの相互作用のダイナミックな性質を理解することは,遺伝子調節機構の解読の鍵です.

研究の目的:

ステロイド受容体の生細胞におけるクロマチンとのダイナミックな結合を視覚化および定量化するために.
クロマチンと核プラズマの間のホルモン占有ステロイド受容体の交換運動を調査する.

主な方法:

マウス乳腺腫瘍ウイルス (MMTV) 要素を組み合わせたレポーターシステムを使用した.
緑色光タンパク質 (GFP) を標識したグルココルチコイド受容体を使用し,生細胞画像撮影を行いました.
クロマチンの受容体ダイナミクスを分析するために光白化実験を行った.

主要な成果:

生きたマウスの細胞におけるMMTV応答要素に対するGFPラベルのグルココルチコイド受容体のターゲティングを成功裏に視覚化しました.
光白化実験では,クロマチン結合状態と核プラズマ状態の間のホルモン占有受容体の急速な交換が示されました.
これは,安定した結合ではなく,非常にダイナミックな相互作用を示しています.

結論:

ステロイド受容体の染色体反応要素への結合は,ダイナミックなプロセスです.
ホルモン占有受容体の急速な交換は,遺伝子調節のより流動的なモデルを強調しています.
この発見は,ホルモンが遺伝子発現をどのように制御するかを理解するための意味を持つ.

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