人間のPAD4は,デメチリミネーション経由でヒストンアルギニンのメチル化レベルを調節する

Yanming Wang¹, Joanna Wysocka, Joyce Sayegh

¹Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.

Science (New York, N.Y.)

|September 4, 2004

まとめ

人間のペプチダリルギニンデミナーゼ4 (PAD4) はヒストンアルギニン残基からメチル群を除去し,シトルリンに変換します. この表遺伝子変異は,特にエストロゲン反応性遺伝子の遺伝子発現を調節する.

科学分野:

エピジェネティクスエピジェネティクス
分子生物学は分子生物学である.
バイオケミストリーバイオケミストリー

背景:

ヒストンのメチル化は遺伝子発現を調節するが,脱メチル化酵素は知られていなかった.
ヒストンのアルギニンメチル化は,表遺伝的遺伝子調節と関連しています.

研究の目的:

ヒストンアルギニン残基をデメチル化する酵素を特定する.
ヒストンアルギニンの脱甲基化と遺伝子調節におけるペプチダリルギニンデミナーゼ4 (PAD4) の役割を調査する.

主な方法:

人間のPAD4.4を用いた酵素解析.
HL-60粒細胞とMCF-7細胞におけるヒストン変異の分析.
ヒストンH3およびH4メチル化およびシトルリン化に対するPAD4の効果を調査する.

主要な成果:

人間のPAD4はヒストンメチアルギニンをシトルリンに変換する酵素として特定されました.
PAD4は,CARM1とPRMT1によってメチル化されたものを含むヒストンH3とH4の複数のアルギニン部位を標的にします.
PAD4の活性により,ヒストンアルギニンメチル化が低下し,HL-60細胞におけるシトルリン化が増加した.
PAD4の活動は,MCF-7細胞におけるエストロゲン反応性遺伝子の転写制御と相関していた.

結論:

PAD4はヒストンアルギニンの甲基化とシトルリン化を調節することによって遺伝子発現を媒介する.
PAD4はヒストン・アルギニンの改変を標的とした新種の表遺伝子調節体を表しています.

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