先駆的な転写因子は,核細胞の部分的なDNAモチーフを標的とし,再プログラムを開始します
Abdenour Soufi1, Meilin Fernandez Garcia1, Artur Jaroszewicz2
1Institute for Regenerative Medicine and Epigenetics Program, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Smilow Center for Translational Research, Building 421, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5157, USA.
Cell
|April 21, 2015
まとめ
先駆的な転写因子 (TF) は,DNA結合ドメインを使用して,静かなクロマチンにアクセスし,細胞命運の変化を開始します. 核子を結合し,表面の部分DNAモチーフを認識する能力は,この重要なプロセスを駆動します.
科学分野:
- 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
- 細胞生物学 細胞生物学
背景:
- パイオニア転写因子 (TFs) は,静かな染色体にアクセスすることによって,細胞命運の変化を開始するために不可欠です.
- よく研究されたパイオニアTFであるFoxAは,翼のヘリックスDNA結合ドメイン (DBD) を使用して,核細胞と圧縮された染色体を結合します.
- 他の先駆的なTFのメカニズムを理解することは,細胞の再プログラムを理解するために不可欠です.
研究 の 目的:
- Oct4,Sox2,Klf4,c-Myc.のヌクレオソームとクロマチンのターゲティング活動を比較するために
- これらの因子の先駆的な活動におけるDNA結合ドメイン (DBDs) の役割を調査する.
- これらの要因がどのように体細胞を複能性へと再プログラムするかを解明する.
主な方法:
- 純化されたOct4,Sox2,Klf4タンパク質によるインビトロ結合測定法.
- In vivoクロマチンのターゲティング分析.
- DNA結合ドメインの構造と機能の比較分析.
主要な成果:
- Oct4,Sox2,Klf4タンパク質は,in vitroで核細胞結合能力を示した.
- これらの要因は, vivoにおいて,優遇的に静かな,ヌクレオソームで濃縮されたクロマチンの部位を標的とした.
- パイオニアの活動は,核細胞の部分DNAモチーフを認識するDBDの能力と相関していた.
- 要素間の座標結合は,部分的なモチーフの認識を容易にする.
結論:
- 先駆的なTFの核細胞を結合し,表面の部分DNAモチーフを認識する能力は,その機能の鍵です.
- これらのメカニズムは,先駆的因子がナイブ染色体にどのようにアクセスし,修正するかを洞察します.
- これらの相互作用を理解することは,細胞の再プログラムと再生医療の進歩に不可欠です.
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