VDJ再結合の発達調節におけるヒストンアセチル化の役割

M T McMurry¹, M S Krangel

¹Department of Immunology, Post Office Box 3010, Duke University Medical Center, Durham NC 27710, USA.

Science (New York, N.Y.)

|January 22, 2000

まとめ

ヒストンのアセチル化は,V(D) J再結合のアクセシビリティを調節する. 強化剤の活動は,発達中のV(D) J再結合に不可欠なヒストンH3の長距離ハイパーアセチル化を誘発する.

科学分野:

分子生物学は分子生物学である.
免疫学免疫学とは
エピジェネティクスエピジェネティクス

背景:

V(D) J再結合は,適応免疫における重要なプロセスであり,強化要素によって発達的に調節される.
増強剤が再結合信号配列のアクセシビリティを制御する正確な分子メカニズムは,ほとんど不明のままである.

研究の目的:

ヒストンの改変,特にヒストンH3アセチル化がV(D) J再結合の調節における役割を調査する.
強化剤の活性がヒストンのアセチル化と再結合部位のアクセシビリティに影響するかどうかを判断する.

主な方法:

レポーター構造体と内生性T細胞受容体アルファ/デルタロカスにおけるヒストンH3アセチル化レベルの測定.
強化剤の活性,ヒストンのアセチル化状態,およびV(D) J再結合効率の間の相関の分析.

主要な成果:

強化剤の活動は,ヒストンH3アセチル化における長距離,発達的に調節された変化を誘導した.
ヒストンH3アセチル化レベルは,V(D) J再結合と密接に相関していることが判明しました.
ヒストンH3のハイパーアセチレーションは,エンハンサー駆動アクセシビリティと併用して観察されました.

結論:

ヒストンH3過酸化は,強化剤の活性とクロマチンのアクセシビリティを結びつける重要な分子機構として提案されています.
このエピジェネティック・モディフィケーションは,V(D) J再結合のための再結合シグナル配列への再結合酵素のアクセスを容易にする.
発見は,免疫受容体遺伝子組成の発達調節についての洞察を提供します.

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