トランスクリプションコファクターは,異なるタイプのコアプロモーターに対して特異性を示す
Vanja Haberle1, Cosmas D Arnold1, Michaela Pagani1
1Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.
Nature
|May 17, 2019
まとめ
転写共因子 (COF) は,異なるプロモータータイプに対する特定の好みを示す. このCOFプロモーターの互換性は,ヒトを含む種間の遺伝子発現プログラムに影響を与えます.
科学分野:
- 分子生物学
- 遺伝学
- エピジェネティクス
背景:
- トランスクリプションコファクター (COF) は,増強剤からプロモーターに信号を伝達することによって,遺伝子発現に不可欠である.
- 以前の研究では,いくつかのCOFが特定のプロモータータイプを好む可能性があるが,COFプロモーター特異性に関する包括的な理解が欠けていた.
研究 の 目的:
- 異なるCOFと様々なコアプロモーター (CP) タイプ間の固有の特異性の程度を調査する.
- COF-プロモーターの互換性が遺伝子調節と転写プログラムに影響を与えるかどうかを決定する.
主な方法:
- Drosophila melanogaster S2細胞で,高通量プロモーター活性アッセイを用いて,72,000の候補核プロモーターに対して23のCOFをスクリーニングした.
- 分析には,異なったCP型に関連した配列要素とクロマチン特性 (H3K4me3,H3K4me1) の特定が含まれていた.
- COFプロモーターとの互換性は,追加のドロソフィラとヒトの細胞系で検証された.
主要な成果:
- COFによるCPの異なる活性化により,COF促進剤との明確な相容れが明らかになった.
- 機能的に異なるCP型は,特定の配列要素 (TATAボックス,DPE,TCT) に対して強化され,ユニークなクロマチンマークを示した.
- COFは,フライとヒトの細胞の両方で,特定のプロモータータイプ (例えば,TATA-boxまたはCpG-島プロモーター) に対する好みを示した.
結論:
- COFプロモーターの互換性は,強化剤が特定の遺伝子セットをどのように活性化させるかを説明する基本的なメカニズムである.
- これらの互換性は,代替プロモーターの使用と遺伝子内の異なった転写開始部位に寄与する.
- COF-プロモーターの相互作用は,ハエから人間への転写プログラムの基礎となる保存された規制原理を表しています.
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