クロマチンのアクセシビリティ 初期のヒト胚の風景と進化との関連
Lei Gao1, Keliang Wu2, Zhenbo Liu1
1CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101 Beijing, China.
Cell
|March 13, 2018
まとめ
クロマチンのアクセシビリティは,ヒトの発達初期に確立され,OCT4はジゴティックゲノム活性化 (ZGA) に重要な役割を果たします. 遺伝子年齢とトランスポゾン活動も初期胚の遺伝子発現の動態に影響します.
科学分野:
- 発達生物学
- エピジェネティクス
- ゲノミクス
背景:
- 初期のヒトの胚形成におけるクロマチンの規制の役割は ほとんど未知のものである.
- 遺伝子調節のダイナミクスを理解することは 発達プロセスにとって極めて重要です
研究 の 目的:
- ヒトの初期胚形成におけるクロマチンアクセシビリティの確立を調査する.
- OCT4のような転写因子の早期発達とジゴティックゲノム活性化 (ZGA) の役割を調査する.
- 遺伝子年齢,プロモーター特性,発現タイミングの関係を理解する.
主な方法:
- DNase I過敏部位 (DHS) 配列は,クロマチンのアクセシビリティをマッピングするために使用されました.
- OCT4結合モチーフの分析とその強化
- 遺伝子年齢とプロモーターのCpG含有量とDHSの確立と遺伝子発現の相関
主要な成果:
- クロマチンのアクセシビリティは,人間の初期の胚形成を通して徐々に確立されます.
- OCT4結合モチーフはヒトのZGAに濃縮され,マウスとは異なり,ヒトのZGAにはOCT4が不可欠である.
- 若い遺伝子と低CpGプロモーターを持つ遺伝子は,後のDHSの確立と発現と関連しており,古い遺伝子は以前のパターンを示しています.
- 活性ヒトトランポゾン (SVA,HERV-K) はDHSを宿し,初期の胚では発現するが,微分化した組織では発現しない.
結論:
- この研究は,人間の初期の発達におけるクロマチンの景観のダイナミックな確立を明らかにしています.
- ZGAにおけるOCT4の種特異的な役割は,発達調節における進化的違いを強調する.
- 遺伝子の年齢とトランスポゾン活動は,胚形成中の遺伝子とトランスポゾン発現を調節する重要な要因であり,進化的発達の視点を提供している.
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