ヒトの転写因子の足跡のグローバル参照マッピング

Jeff Vierstra¹, John Lazar^2,3, Richard Sandstrom²

¹Altius Institute for Biomedical Sciences, Seattle, WA, USA. jvierstra@altius.org.

Nature

|July 31, 2020

まとめ

この研究はDNA I足跡を用いてヒトゲノムの何百万もの転写因子結合部位をマッピングしています遺伝子変異は遺伝子調節と人間の特徴に大きく影響します

科学分野:

ゲノミクス
分子生物学
エピジェネティクス

背景:

DNAに結合する転写因子は遺伝子発現を調節する.
制御DNAの遺伝的変異は病気や特徴と関連しています
機能的な規制変数を特定するのは難しい.

研究の目的:

複製因子の足跡をヒトゲノム全体に包括的にマッピングする.
遺伝子調節におけるDNAアクセシビリティと転写因子の占有率の役割を理解する.
遺伝子変異が規制要素に与える影響を調査する.

主な方法:

243種類のヒト細胞/組織から高密度のDNase I分裂マップを生成した.
核酸分辨率で何百万もの転写因子占有部位を区切るための統合データ.
遺伝子変異,足跡,規制要素のアクセシビリティとの関係を分析した.

主要な成果:

ゲノム全体で約450万の転写因子占有部位を図示した.
差異的なTF占有率ではなく,主にDNAアクセシビリティによって調節されていることを発見しました.
病気に関連した変異が足跡の中で濃縮され,ほぼ同じ機能の喪失/獲得アレルを持つことが示されました.
足跡内の遺伝的多様性の密度が増加し,シス調節進化の役割を示唆した.

結論:

転写因子結合部位の高解像度マップを提供します.
遺伝子規制メカニズムと機能的な遺伝子変異を分析するための枠組みを提供します.
人間の病気と進化を理解する上で規制の足跡の重要性を強調する.

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