ヒストンの改変をヒトの親子から生殖細胞への移行時にリセットする

Weikun Xia¹, Jiawei Xu², Guang Yu¹

¹Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.

Science (New York, N.Y.)

|July 6, 2019

まとめ

ヒトの早期発達にはヒストンの重要な変化が伴う. 研究者はトリメチル化ヒストンH3ライシン4 (H3K4me3) とH3K27me3のパターンを卵細胞と胚にマッピングし,重要な表遺伝子プリミング段階を明らかにした.

科学分野:

エピジェネティクスと発達生物学
人間の胚
ゲノミクス

背景:

ヒストンの改変は遺伝子発現と胚発達の重要な調節因子である.
ヒトの早期発達における表遺伝的再プログラムを理解することは,生殖医学と発達研究にとって不可欠です.

研究の目的:

ヒト卵細胞の成熟と胚の発達初期における重要なヒストンマーク,特にH3K4me3とH3K27me3の再プログラミングを調査する.
染色体状態の動的変化と,卵細胞から移植前の胚への遺伝子発現との関係を特徴づける.

主な方法:

ヒトの卵細胞と初期胚の染色体分析
ヒストンの改変 (H3K4me3,H3K27me3) をマッピングするための高通量配列化.
エピジェネティック状態と遺伝子の活性を相関させるトランスクリプトーム分析.

主要な成果:

人間の卵子細胞は,マウスの卵子細胞とは異なる,主に正規のH3K4me3パターンを示しています.
授精後,胚は許容性クロマチンを獲得し,H3K4me3は広く広がり,H3K27me3は全般的に枯渇する.
遺伝子の活性化後の活性化と抑制状態の間のCpG豊富な調節領域の移行,H3K27me3の発達遺伝子の回復.
クロマチンとトランスクリプトームのデータを統合すると,初期の系統の仕様で転写回路と非対称なH3K27me3パターンが明らかになった.

結論:

ヒトの早期発達には,親からジゴティックへの表遺伝的移行を橋渡しする明確な"プリミングフェーズ"が含まれる.
H3K4me3とH3K27me3の動的調節は,ヒト胚の発達軌跡を確立するために重要である.
これらの発見は,ヒトの胚形成を統括する副遺伝的景観に関する新しい洞察を提供しています

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