DNA修復複合体は,胚性幹細胞におけるOct4/Sox2共同活性化剤として機能する
Yick W Fong1, Carla Inouye, Teppei Yamaguchi
1Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|October 4, 2011
まとめ
研究者らは,XPC-ヌクレオチド切除修復複合体 (XPC-nucleotide excision repair complex) として知られる幹細胞共活性化複合体 (SCC) を発見し,胚幹細胞の多能性および再プログラミングを維持するために決定的な役割を果たした. この複合体は,多能性に関与する重要な遺伝子を活性化するために不可欠です.
科学分野:
- * 分子・細胞生物学
- * 幹細胞生物学について
- * エピジェネティクスと遺伝子調節
背景:
- * 胚性幹細胞 (ES細胞) は多能性を持ち,すべての細胞タイプに分化する能力を持っています.
- * 転写活性化剤Oct4,Sox2およびNanogは,多能性の重要な調節剤である.
- * 同活性化剤は,これらの転写因子の機能を媒介する上で重要な役割を果たします.
研究 の 目的:
- * 多能性のためのOct4/Sox2媒介遺伝子発現プログラムに関与する新種の共活性剤を特定する.
- * 新しく発見された幹細胞共活性化複合体 (SCC) の機能と作用機構を特徴づける.
主な方法:
- *SCC.を検出するために,無偏見の in vitro トランスクリプション-生化学補完測定法を使用しました.
- * SCCの成分を特定するために,浄化,質量スペクトロメトリー,再構成を活用しました.
- * Oct4/Sox2とのSCCの相互作用と,ChIP-seq.を用いた標的遺伝子プロモーターへのSCCの誘導を調査した.
- *SCC減少がES細胞の多能性と体細胞再プログラムに与える影響を評価した.
主要な成果:
- * Oct4とSox2.2によるナノグ遺伝子の相乗活性化に不可欠なマルチサブユニット幹細胞共活性化複合体 (SCC) が発見された.
- * SCCは,トリミラーXPC-ヌクレオチド切除修復複合体として識別されました.
- *SCCとOct4およびSox2との直接の相互作用と,多能性遺伝子プロモーターへのSCCの誘導が実証された.
- * SCC/XPCの枯渇は,ES細胞の多能性および体細胞の再プログラミングを誘発性多能性幹細胞 (iPS) に低下させることを示した.
結論:
- *XPC-ヌクレオチド切除修復複合体は,重要な幹細胞共同活性化剤 (SCC) として機能する.
- *SCCは,胚性幹細胞の多能性を維持し,体細胞の再プログラムを促進する上で重要な役割を果たします.
- *この発見は,トランスクリプションの調節とゲノムの完全性におけるXPC複合体の二重の役割を明らかにしています.
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