単細胞クロマチンのアクセシビリティは,規制変異の原理を明らかにします

Jason D Buenrostro¹, Beijing Wu², Ulrike M Litzenburger³

¹1] Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA [2] Program in Epithelial Biology and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA.

Nature

|June 18, 2015

まとめ

この研究は,DNAの調節変異が細胞間違いを生じさせる方法を明らかにしています. 新しい単細胞法では,ゲノムアクセシビリティをマップし,細胞の多様性と3Dゲノム組織を制御する要因を明らかにします.

科学分野:

ゲノミクスゲノミクスとは
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:

細胞間の多様性は生物学において極めて重要であり,発達や病気に影響を及ぼします.
同様のDNAからこのような変異を生成するメカニズムは十分に理解されていません.

研究の目的:

単細胞レベルでDNAの調節変異をマッピングする.
哺乳類DNAの調節変異を制御する原理を特定する.

主な方法:

配列 (ATAC-seq) を用いたトランポゼーゼアクセシブルクロマチンの測定を統合したマイクロ流体学プラットフォームを開発しました.
単細胞ATAC-seq (scATAC-seq) を適用して,個々の細胞ゲノムをプロファイルしました.
トランスファクターとシス要素に関連したアクセシビリティの分散を分析した.

主要な成果:

scATAC-seqプロフィールは,大部分の ATAC-seq を反映し,細胞間変化の洞察を提供します.
変性を誘発または抑制するトランスファクターを特定した.
細胞型特異的な変動パターンを発見し,それを3Dゲノム組織と関連付けました.

結論:

単細胞DNAのアクセシビリティ分析は",ルゲルーム"に関する新しい洞察を提供します.
このアプローチは,細胞の異質性を駆動する基本的なメカニズムの理解を進めます.

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