プレースホルダー核細胞は,生殖細胞から胚へのDNAメチル化再プログラムを基にしています
Patrick J Murphy1, Shan Fu Wu1, Cody R James1
1Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Cell
|February 20, 2018
まとめ
ヒストンH2A変種H2A.Z.FVとH3K4me1を含むプレイスホルダーヌクレオソームは,斑馬魚の胚におけるDNAメチル化を防止する. この表遺伝的メカニズムは,初期の発達と遺伝の間に遺伝子の活性化や抑制を制御する.
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:
- エピジェネティックマークは 生殖細胞から胚への移行を導いて 幹細胞のプログラムと遺伝に影響を与えます
- ゼブラフィッシュでは,静止状態の胚でDNAメチル化が確立され,父親のパターンが維持され,母親のパターンが再プログラムされる.
- これらの表遺伝的変化を制御するメカニズムを理解することは,発達生物学にとって極めて重要です.
研究 の 目的:
- 斑馬魚の生殖線から胚への移行中にDNAメチル化パターンがプログラムされるメカニズムを解明する.
- DNAメチル化と遺伝子発現を調節する特定の核細胞の役割を特定する.
- エピジェネティック・マークを 破壊した結果について調べる
主な方法:
- クロマチン免疫降水 (ChIP) により,核細胞の占有率とヒストンの変化を特定する.
- ゲノム全体のメチル化パターンを評価するDNAメチル化分析
- 遺伝子発現とDNAメチル化に対する核分裂の影響を研究するための機能検査.
主要な成果:
- H2A.Z (FV) とH3K4me1を含む"置換体"ヌクレオソームは,精子と分裂胚のDNAメチル化フリー領域を占める.
- これらの核細胞は 家庭管理のプロモーターや 初期の胚の遺伝子で発見されます
- プレースホルダーを失うとDNAメチル化が蓄積され,増やすと低メチル化と異常な遺伝子活性化が生じます.
結論:
- プレイスホルダー核細胞は,静止状態の発達段階でDNAメチル化を積極的に阻害する.
- このメカニズムは,トランスクリプションの初期に 活性化または抑制のために親の遺伝子をバランスします.
- プレースホルダー核細胞は,ゼブラフィッシュの発達初期における表遺伝的再プログラムと遺伝子発現の重要な調節因子である.
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