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ホメオドメインを含む組織特異の転写因子は,下垂体フェノタイプを特定する
H A Ingraham1, R P Chen, H J Mangalam
1Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla 92093.
Cell
|November 4, 1988
まとめ
新しく特定された下垂体特異的転写因子Pit-1は,ネズミのプロラクチンと成長ホルモン遺伝子を調節するDNA要素と結合する. Pit-1はこれらの遺伝子を非下垂体細胞で活性化させ,下垂体細胞発達の役割を示唆する.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- 発達生物学 発達生物学とは
背景:
- 細胞特異的な遺伝子発現は,組織発達に不可欠である.
- ネズミのプロラクチン遺伝子は,下垂体細胞で活性化するために特定のシス活性元素を必要とします.
研究 の 目的:
- pituitary-specific遺伝子の活性化に責任を負う転写因子を特定し,特徴づけること.
- pituitary細胞のフェノタイプを授与するこの因子の役割を調査する.
主な方法:
- ネズミのプロラクチンおよび成長ホルモン遺伝子におけるAT豊富な元素との結合に基づくPit-1補完DNAのクローン化.
- ヘテロログのHeLa細胞におけるPit-1の発現.
- 保存ドメインのPit-1タンパク質構造の分析.
主要な成果:
- 33 kdのタンパク質であるPit-1が特定され,ドロソフィラホメオドメインとの類似性を示した.
- Pit-1 mRNAは,前垂体体ソマトトロフ細胞と乳トロフ細胞にのみ発現する.
- HeLa細胞におけるPit-1発現は,プロラクチンと成長ホルモンの融合遺伝子発現を活性化させた.
結論:
- Pit-1は,プロラクチンおよび成長ホルモン遺伝子の調節に不可欠な,下垂体特異的転写因子です.
- Pit-1は,下垂体細胞のフェノタイプを与えるのに十分であり,下垂体発達における重要な役割を果たしていることを示しています.
- メタゾアにおける組織特異的なフェノタイプは,ドメインが保存された転写因子の家族によって制御されることがあります.
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