超ヒアズマ的昼間時計からのリズム的出力を調節する分子機構
X Jin1, L P Shearman, D R Weaver
1Pediatric Service, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Cell
|February 16, 1999
まとめ
核の分子時計は,脳内のアルギニン・バソプレシン遺伝子の毎日のリズムを直接制御する. 時計遺伝子を破壊すると,血管圧縮素のリズムがなくなり,ペプチドレベルに影響を与えます.
科学分野:
- 神経科学は神経科学である.
- クロノバイオロジー クロノバイオロジー
- 分子生物学は分子生物学である.
背景:
- ネズミのスプラキアスマティック核 (SCN) は昼夜リズムを生成する.
- CLOCK,BMAL1,mPer遺伝子を含むコアトランスクリプションフィードバックループがSCNクロックを調節する.
研究 の 目的:
- SCN内の時計制御された出力であるアルギニンバソプレシン (AVP) 遺伝子の転写調節を調査する.
- AVPの遺伝子発現リズムを調節するコアクロックコンポーネントの役割を明らかにする.
主な方法:
- 野生型およびクロック/クロック変異マウスの遺伝子発現リズム分析.
- ルシフェラーゼレポーター遺伝子解析は,CLOCK-BMAL1ヘテロダイマーによる転写活性化を評価する.
主要な成果:
- mPer遺伝子のRNAリズムが,クロック/クロックマウスで著しく鈍化していた.
- ワソプレシンRNAリズムがクロック/クロックマウスで廃止され,ペプチドレベルが低下した.
- CLOCK-BMAL1ヘテロダイマーは,mPERとmTIMによって抑制されるEボックスの強化剤を介してバソプレシン転写を活性化します.
結論:
- 核の分子時計機構は,アルギニン・バソプレシンなどの時計制御された出力リズムを直接調節する.
- CLOCK-BMAL1ヘテロダイマーは,バソプレシンリズムの重要な陽性調節剤である.
- mPERおよびmTIMタンパク質は,この転写フィードバックループの負の調節体として作用します.
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