ランダムとインプリントされたXist発現は,先制メチレーションによって制御されるという証拠

D P Norris¹, D Patel, G F Kay

¹Section of Comparative Biology, Medical Research Council Clinical Research Centre, Harrow, England.

Cell

|April 8, 1994

まとめ

DNAメチル化パターンは,Xist遺伝子を調節し,X染色体の不活性化を制御する. Xistの微分メチル化がXistの発現に先行し,遺伝子の静止に影響を与えます.

科学分野:

エピジェネティクスエピジェネティクス
ゲノミクスゲノミクスとは
発達生物学発達生物学について

背景:

Xist遺伝子は,X染色体の不活性化において決定的な役割を果たし,女性のX染色体の1つを静止させます.
Xist発現を制御するエピジェネティックメカニズムを理解することは,X不活性化の開始を解読する鍵です.

研究の目的:

マウスXist遺伝子の発現を調節するDNAメチル化の役割を調査する.
メチル化パターンが,異なる組織および発達段階におけるXist発現とどのように相関するかを決定する.

主な方法:

体組織,インプリント組織,および男性生殖系統におけるXistアレルメチレーション状態の分析.
胚性幹細胞におけるX不活性化初期におけるXist遺伝子発現とメチル化パターンの相関.

主要な成果:

ソマティック組織はXistアレルの微分メチル化を示す:活性Xでメチル化,非活性Xで非メチル化.
インプリントされたX不活性化には,非メチル化された父性Xistおよびメチル化された母性Xistアレルが含まれます.
Xistの脱メチル化は,雄性半導体分裂の間に発生し,精子に持続し,潜在的に父子の表現をインプリントする.
微分Xistメチレーションは,胚性幹細胞の微分化におけるX不活性化初期における発現に先行する.

結論:

DNAメチル化は,Xist遺伝子発現とX染色体不活性化の重要な調節因子である.
Xistのメチル化パターンは,発達期および生殖細胞で動的に制御されます.
これらの発見は,用量補償とゲノムインプリントの表遺伝子制御に関する洞察を提供します.

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