系統特異の転写サイレンサーは,Tリンパ球発達の過程でCD4遺伝子発現を調節する

S Sawada¹, J D Scarborough, N Killeen

¹Department of Microbiology and Immunology, University of California, San Francisco 94143-0414.

Cell

|June 17, 1994

まとめ

研究者らは,発達中のT細胞におけるCD4遺伝子発現を制御する規制DNA領域を特定した. このサイレンスエレメントは,T細胞の分化をヘルパーまたは細胞毒性系に導くために非常に重要です.

科学分野:

免疫学免疫学とは
発達生物学発達生物学について
分子遺伝学分子遺伝学

背景:

Tリンパ球の分化には,CD4およびCD8核受容体の異なる発現が含まれます.
ヘルパーまたは細胞毒性系へのコミットメントには,CD4またはCD8の選択的な静止が求められます.
CD4およびCD8発現を制御する規制メカニズムを理解することは,T細胞の発達に不可欠です.

研究の目的:

Tリンパ球発達の過程でCD4遺伝子発現を制御する規制要素を特定する.
CD4遺伝子ロカス内の新しい調節領域の機能と特性を特徴付ける.
この地域のT細胞系統における役割を調査する.

主な方法:

遺伝子調節を研究するために,トランスジェニックマウスモデルを使用した.
特定された規制領域によって制御されるトランスゲンの発現パターンを分析した.
異なるチモサイトサブセットにおける遺伝子発現に対する規制領域の影響を評価した.

主要な成果:

CD4-CD8+チモサイトにおけるCD4トランスゲン発現を選択的に抑制するイントロニク調節領域を特定しました.
この領域が未成熟のCD4-CD8-チモサイトの発現を抑制することも示された.
調節要素は,方向と位置にかかわらず機能し,異質な配列に作用することを示した.
酵母とドロソフィラのサイレンサーに似た性質を持つ強力な転写サイレンサーとして特徴付けました.

結論:

CD4遺伝子は,CD4-CD8-からCD4+CD8+シモサイトへの微分化中に減圧されます.
新しい,発達的に調節された脊椎動物の転写サイレンサーは,CD4発現を制御します.
この静音器は,CD4発現を調節することによって,T細胞系統の結合に重要な役割を果たします.

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