遺伝子静止とヒストンH3K9メチル化によるDNA配列依存の表遺伝

Xiaoyi Wang¹, Danesh Moazed²

¹Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Science (New York, N.Y.)

|March 18, 2017

まとめ

分裂酵母における表遺伝子遺伝は,安定した遺伝子静止のために特定のDNA配列を必要とします. Epe1p酵素を削除すると,ATF/CREB転写因子結合部位に依存する静止状態の継承が可能になります.

科学分野:

分子生物学
エピジェネティクス
遺伝学

背景:

エピジェネティック継承は遺伝子発現の細胞記憶を維持する.
ヒストンH3ライシン9メチル化 (H3K9me) は,分裂酵母におけるヘテロクロマチンを示す.
Epe1p酵素の削除は,H3K9meの表遺伝子遺伝を促進する.

研究の目的:

Epe1pが欠けている分裂酵母で,先天的な表遺伝子状態が安定的に維持される方法を調査する.
cis-遺伝性H3K9me依存性サイレンシングにおけるDNA配列とゲノム文脈の役割を検証する.

主な方法:

シス-遺伝性H3K9me依存性静音化を研究するシステムを開発した.
エピジェネティック継承におけるDNA配列とゲノム文脈の役割を分析した.

主要な成果:

epe1+細胞における静音化の表遺伝子遺伝は,配列独立のH3K9meの増殖を伴う.
遺伝には,転写因子 (ATF) -アデノシン3',5'-モノフォスファート (cAMP) 応答要素結合タンパク質 (CREB) 家族の転写因子を活性化するための結合部位が必要です.
本来の染色体内の特定のDNA配列は,H3K9meのシス継承に不可欠です.

結論:

特定のDNA配列は,H3K9meのシス遺伝と静かな表遺伝状態に寄与する.
配列依存の転写因子結合は,分裂酵母における安定した表遺伝子記憶に不可欠である.

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