人間 の 遺伝子 の 内面 の 動 力 は,表現 の 異質 性 の 基礎 を 明らかに し て い ます
Joseph Rodriguez1, Gang Ren2, Christopher R Day1
1Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Bethesda, MD, USA.
Cell
|December 18, 2018
まとめ
ヒトの遺伝子発現は 安定した状態ではなく 変化する不活性期間のせいで騒々しくなります この研究は 遺伝子調節,染色体構造,細胞反応を エストロゲンシグナル伝達と結びつけています
科学分野:
- 分子生物学
- ゲノミクス
- 細胞生物学
背景:
- メタゾアンの転写調節には,増強剤とプロモーターの間の長距離ゲノム接触が含まれます.
- ほとんどの遺伝子はエピソディックなRNA合成を 発現し,これはトランスクリプション・バーストとして知られています.
研究 の 目的:
- ゲノムとの接触,トランスクリプションの破裂,そしてダイナミックな遺伝子調節の関係を調査する.
- 生細胞画像と染色体構成のキャプチャを使用して,エストロゲン反応性TFF1遺伝子の内生調節を解剖する.
主な方法:
- 活細胞RNA画像は内生的な遺伝子転写の動態を監視する.
- 3次元ゲノム構造を分析する Hi-C 測定
- 転写,染色体構造,信号感知に関する数学的モデリング.
主要な成果:
- TFF1遺伝子の短い活性転写期と変数不活性期 (数分から数日) を観察した.
- 不活性期における異質性が遺伝子発現ノイズとタンパク質レベル分布を説明することを示した.
- TFF1は高度に誘発されるが,ダイナミックな転写突起を示すことが示された.
結論:
- 遺伝子発現の"騒音"は 安定した生物学的状態ではなく ダイナミックな転写の変動から生じる.
- エストロゲンのような信号に対する 細胞の反応には 転写突発のダイナミックな調節が含まれます
- 数学的モデルは染色体構造,遺伝子活動,シグナル誘発の転写ダイナミクスを関連付けることができます.
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