アレル特異の表遺伝子図は,配列依存のストキャスティックスイッチングをレギュレータロシウムで明らかにする
Vitor Onuchic1,2,3,4, Eugene Lurie1,3,4, Ivenise Carrero1,3
1Molecular and Human Genetics Department, Baylor College of Medicine, Houston, TX, USA.
Science (New York, N.Y.)
|August 25, 2018
まとめ
調節性DNAの遺伝的変異は,DNAメチル化のような表遺伝的マークを変化させることで健康に影響します. この研究はこれらの不均衡をマッピングし,表遺伝子変異,遺伝子調節,疾患リスクとの関係を明らかにしています.
科学分野:
- ゲノミクス
- エピジェネティクス
- 人間 の 健康
背景:
- 遺伝的変異は 規制要素を通して 人間の健康に影響を与えます
- DNAメチル化とヒストンのマークを含む表遺伝的変異は,遺伝子調節において重要な役割を果たします.
- 遺伝的変異と表遺伝学の相互作用を理解することは 病気のメカニズムを解読する鍵です
研究 の 目的:
- 多様なヒトの細胞と組織で 遺伝的不均衡の高解像度マップを作成する
- 遺伝子変異,DNAメチル化,ヒストン変異,遺伝子転写の関係を調査する.
- エピジェネティック・アレル不均衡,ストキャスティック・スイッチング,疾患関連遺伝的変異を結びつける統一モデルを開発する.
主な方法:
- 13人のドナーの36種類の細胞/組織から71の表遺伝子組の構築.
- メチローム49の全ゲノムビスルフィート配列解析
- DNAメチル化,ヒストンマーク,およびヘテロジゴス調節部位における遺伝子転写の分析
主要な成果:
- 配列に依存するCpGメチル化不均衡を持つ数千の調節部位を特定した.
- これらの場所でのストキャスティックスイッチング (ランダムなメチル化状態の移行) の濃縮が観察されました.
- メチル化不均衡は,アレル特異的なメチル化周波数によって説明されていることが示された.
- アレル性表遺伝子不均衡,ストキャスティックスイッチング,疾患遺伝子を結びつけるモデルを開発した.
結論:
- DNAメチル化とヒストンの配列依存性不均衡は,ヒトの調節部位に多く見られる.
- ストキャスティック・スイッチングは遺伝子調節部位における表遺伝的変異に寄与する.
- この表遺伝的変異は,ヒトの病気に関連する遺伝的変異と関連しています.
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