PTIPは,免疫グロブリンクラス・スイッチ・リコンビネーションにとって重要なクロマチンの変化を促進します

Jeremy A Daniel¹, Margarida Almeida Santos, Zhibin Wang

¹Experimental Immunology Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Science (New York, N.Y.)

|July 31, 2010

まとめ

DNA修復に不可欠なタンパク質であるPTIPは,DNAのアクセシビリティを制御することによって,免疫グロブリンクラスの切り替えを調節する. その欠如は,抗体機能とゲノム安定性を損なう.

科学分野:

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

背景:

リンパ球におけるプログラムされた遺伝的再編成は,DNAの二重鎖断裂 (DSB) 形成のための転写に依存する.
抗原受容体遺伝子転写は,DNA再結合および修復プロセスにとって不可欠です.

研究の目的:

免疫グロブリン重鎖 (Igh) 局所調節におけるMLL3-MLL4複合体におけるPTIPの役割を調査する.
免疫グロブリンクラスの切り替えとゲノム安定性におけるPTIPの機能を決定する.

主な方法:

PTIP欠乏した活性化されたB細胞の分析.
ヒストン3ライシン4トリメチル化 (H3K4me3) とIgh位置での転写開始の評価.
DSBの修復とクラススイッチ再結合 (CSR) のPTIPの役割の評価.

主要な成果:

活性化されたB細胞におけるPTIP欠乏は,H3K4me3の減少とIgh場所での転写開始障害をもたらした.
PTIPの喪失は,欠陥のある免疫グロブリンクラスの切り替えにつながった.
DSBにおけるPTIP蓄積は,Ighスイッチトランスクリプションとは独立してCSRとゲノム安定性にとって不可欠であることが判明しました.

結論:

PTIPは,CSRのIgh locusアクセシビリティを調節する重要なクロマチンの修正を促進します.
MLL3-MLL4複合体は,PTIP経由で,抗体エフェクター機能を調節する非冗長な役割を果たします.

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