合成の逆行配列はデフォルトのゲノム状態を明らかにする

Brendan R Camellato¹, Ran Brosh¹, Hannah J Ashe¹

¹Institute for Systems Genetics, NYU Langone Health, New York, NY, USA.

Nature

|March 6, 2024

まとめ

合成DNA配列はイーストでは活性ですがマウス細胞では無活性であり既定のゲノム状態の違いを明らかにしていますこれは単なる騒音という普遍的な転写の概念に挑戦し遺伝子の進化にも影響を及ぼします

科学分野:

ゲノミクス
分子生物学
進化生物学

背景:

普遍的な転写活動は種間で共通する特徴であるが,その起源 (選択対ノイズ) は議論の余地がある.
既定のゲノム状態を理解することは,広範囲にわたる転写の生物学的意義を決定するために重要です.

研究の目的:

進化したコーディングや規制情報のない合成ゲノム配列が転写活動を示すかどうかを調査する.
Saccharomyces cerevisiae (酵母) とMus musculus (マウス) の胚性幹細胞の"デフォルトゲノム状態"を比較する.

主な方法:

ヒトのHPRT1を逆転した合成101kbロクスを酵母とマウスのゲノムに導入.
両種の合成ロカスにおけるゲノム活動とクロマチンシグネチャーの特徴
活性への影響を評価するために,CpGダイヌクレオチドが欠けている変異体の分析.

主要な成果:

酵母では,ネイティブのプロモーターがなくても,合成ロクスの広範な転写活動が観察されました.
マウスの胚性幹細胞では,合成ロカスが転写的に不活性であり,抑圧的なクロマチンシグネチャーを示した.
CpGが欠乏した変種は,マウスの細胞では,抑制シグネチャーが緩和されたにもかかわらず,転写的に不活性であった.

結論:

合成の非コーディングDNA配列は,マウス細胞と酵母細胞の異なった転写行動を示し,異なったデフォルトゲノム状態を示しています.
これらの発見は,広範囲の転写が単なる"騒音"ではなく,水平遺伝子の移転と新しい遺伝子の出現に影響を及ぼすことを示唆しています.

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