人間に保存された非コーディング配列のインビヴォ強化剤分析
Len A Pennacchio1, Nadav Ahituv, Alan M Moses
1US Department of Energy Joint Genome Institute, Walnut Creek, California 94598, USA. LAPennacchio@lbl.gov
Nature
|November 7, 2006
まとめ
研究者らは,進化的保存を用いた遺伝子調節要素を特定した. 多くの保存された配列は,特に発達中の神経系において,強化剤として機能し,ゲノムアノテーションを支援します.
科学分野:
- ゲノミクスゲノミクスとは
- 発達生物学 発達生物学について
- 進化生物学の進化生物学について
背景:
- 遺伝子調節要素を特定することは,脊椎動物のゲノムアノテーションにとって極めて重要です.
- 実験的に検証されたトレーニングセットの欠如は,遺伝子調節機能の定義における進歩を阻害しています.
研究 の 目的:
- ヒトゲノム内の保存された非コーディング要素のインビボ強化活性を特定し,特徴づけること.
- 特徴づけられたヒト遺伝子増強剤のカタログを拡大し,検証されたトレーニングセットを作成する.
主な方法:
- 極端な進化的シーケンス保存 (人間-パッファーフィッシュ,人間-マウス-ラット) を利用して,推定遺伝子の規制要素をフィルタリングしました.
- トランスジェニックマウスエンハンサーアッセイを用いて,胚の日11.5.5で,高度に保存された167の非コーディング配列をテストした.
主要な成果:
- テストされた保存された配列の45%は,組織特異の強化剤として再現的に機能した.
- 特定された増強剤のほとんどは (75) 発達中の神経系,特に前頭脳に遺伝子発現を誘導した.
- 前頭脳のターゲティング要素で強化されたシーケンスのシグネチャーにより,予測の精度が向上しました.
結論:
- 進化的保存は,機能的な遺伝子増強剤を特定するための強力なフィルターです.
- この研究は,特徴づけられたヒト強化剤のレパートリーを大幅に拡張し,貴重なトレーニングデータを提供します.
- この発見は,ヒトゲノムの規制語彙の解読を容易にし,様々な生物学的応用をサポートします.
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