ヒトゲノムのアクセシブルなクロマチンの風景
Robert E Thurman1, Eric Rynes, Richard Humbert
1Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
Nature
|September 8, 2012
まとめ
数百万のDNAse I過敏部位 (DHSs) をマッピングし,新しい調節性DNA要素とその細胞特異的な機能を明らかにしました. この地図は,規制地域とプロモーターをリンクし,クロマチンのアクセシビリティとヒトの遺伝的多様性との関係を明らかにします.
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
- 規制生物学 規制生物学とは
背景:
- DNAse I過敏部位 (DHSs) は,調節性DNAの重要なマーカーであり,強化剤やプロモーターなどの要素を識別します.
- 以前の研究では,DHSをマッピングしましたが,多様なヒト細胞タイプにわたる包括的でゲノム全体の地図は欠けていました.
研究 の 目的:
- 125の多様な細胞および組織タイプにわたるヒトDHSの最初の広範なゲノム幅の地図を作成する.
- 新規の規制要素を特定し,それらの細胞選択的調節と機能的関係を理解する.
主な方法:
- 125種類のヒトの細胞と組織でDHSを特定するための全ゲノムプロファイリング.
- ENCODEデータを用いて,クロマチンのアクセシビリティ,転写,DNAメチル化,および調節因子の占有率との関係を分析する解説.
- 遠隔DHSをターゲットプロモーターと接続し,共活性化要素を特定するための計算分析.
主要な成果:
- 約290万のDHSを特定し,既知の調節配列をカバーし,多数の新しい細胞選択要素を明らかにしました.
- クロマチンのアクセシビリティ,転写,DNAメチル化,および調節因子結合の間の新しいリンクを確立しました.
- ~580,000の遠隔DHSをターゲットプロモーターと接続し,共活性化要素の体系的なペアリングと組織的なパターンを明らかにしました.
- DHSパターンが細胞タイプ特有の機能を予測することを実証し,多能細胞におけるDHS,変異率,およびヒトの多様性との関連を特定しました.
結論:
- 総合的なDHSマップは,CIS規制要素とその機能の発見と理解のための豊富なリソースを提供します.
- クロマチンのアクセシビリティパターンは組織化され,細胞機能の予測であり,ヒトの遺伝的変異と進化に影響を及ぼします.
関連する概念動画
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01:01Euchromatin
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Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
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02:38Heterochromatin
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02:38Heterochromatin
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Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
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01:32Chromatin Packaging
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