CpG島は,CpG結合タンパク質Cfp1を通じてクロマチンの構造に影響を与えます

John P Thomson¹, Peter J Skene, Jim Selfridge

¹Wellcome Trust Centre for Cell Biology, Michael Swann Building, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, UK.

Nature

|April 16, 2010

まとめ

CpG島 (CGI) は,重要なゲノム領域である. この研究は,Cfp1を非メチル化CpGと結合し,染色体構造とH3K4me3レベルに影響を与え,遺伝子発現を調節するタンパク質として識別しています.

科学分野:

ゲノミクスゲノミクスとは
エピジェネティクスエピジェネティクス
分子生物学は分子生物学である.

背景:

CpG島 (CGI) は,高CpG二核酸密度を持つGC豊富なゲノム領域である.
ほとんどのヒトの遺伝子プロモーターはCGI内にあり,通常は非メチル化であり,H3K4me3.3でマークされています.
染色体構造と転写における非メチル化CGIの機能的役割は不明である.

研究の目的:

非メチル化CpG群島の機能的重要性を調査する.
非メチル化CpG部位に特異的に結合するタンパク質を特定する.
クロマチンの改変を確立する際にCpG結合タンパク質の役割を理解する.

主な方法:

すべてのCGIに共通するタンパク質のバイオ情報検索.
非メチル化CpGを用いたCfp1に対するインビトロ結合測定法.
染色体免疫降水 (ChIP) と高通量シーケンス.
マウスゲノムに統合された人工CpGクラスターの分析.

主要な成果:

Cfp1は,CGIで高度に濃縮されたタンパク質として特定され,CpGをインビトロとインビヴォの両方で選択的に結合します.
Cfp1結合はマウス脳における非メチル化CGIとH3K4me3サイトと強く相関していた.
Cfp1の枯渇は,CGIにおけるH3K4me3のレベルを低下させ,H3K4メチルトランスフェラーゼの徴募におけるその役割を示した.
人工CpGクラスターは,Cfp1を勧誘し,H3K4me3を誘導した.

結論:

非メチル化CpG島は,局所クロマチンの改変状態を誘導する上で重要な役割を果たします.
Cfp1は重要なメディエーターであり,非メチル化CGIとH3K4トリメチル化を結びつける.
これらの発見は,CGIが染色体構造と潜在的に遺伝子調節に影響を与えるメカニズムを明らかにしています.

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