LSD1は,アンドロゲン受容体依存転写を促進するために,抑制性ヒストンのマークをデメチラ化します
Eric Metzger1, Melanie Wissmann, Na Yin
1Universitäts-Frauenklinik und Zentrum für Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
Nature
|August 5, 2005
まとめ
リシン特異性デメチラーゼ1 (LSD1) はアンドロゲン受容体と相互作用し,前立腺細胞における遺伝子転写と細胞増殖を活性化します. パルギリンでLSD1を阻害すると,これらの効果が阻害され,新たな治療戦略が提供されます.
科学分野:
- 分子生物学は分子生物学である.
- エピジェネティクス エピジェネティクス
- がん生物学 がん生物学
背景:
- ユカリオットの遺伝子調節には,クロマチンの変形剤とアンドロゲン受容体のような転写因子が含まれています.
- 特定のライシン残基におけるヒストンのメチル化状態は,遺伝子の活性化と抑制を調節する.
研究 の 目的:
- 前立腺細胞におけるアンドロゲン受容体媒介遺伝子調節におけるリジン特異性デメチラーゼ1 (LSD1) の役割を調査する.
- LSD1の活性がアンドロゲン受容体の機能を制御するために調節できるかどうかを判断する.
主な方法:
- 前立腺組織におけるLSD1とアンドロゲン受容体の共局所化研究.
- インビトロとインビボの相互作用アッセイ.
- アンドロゲン受容体依存転写アッセイ.
- クロマチン免疫プレシピテーション (ChIP) 分析.
- LSDのノックダウン研究1.1.
- パルギリンを使用したLSD1の阻害.
主要な成果:
- LSD1は,正常な前立腺細胞と腫瘍前立腺細胞のアンドロゲン受容体と共局し,相互作用する.
- LSD1はアンドロゲン受容体に依存した転写と細胞増殖を刺激する.
- LSD1のノックダウンは,アンドロゲン誘発の転写活性化と増殖を無効化する.
- LSD1は,アンドロゲン受容体と,リガンド依存のクロマチン複合体を形成する.
- LSD1はヒストンH3をライシン9 (H3-K9) にデメチラ化し,抑制マークを和らげ,標的遺伝子を抑制する.
- パルギリンはLSD1の活性を抑制し,H3-K9の脱メチル化とアンドロゲン受容体依存転写を阻害する.
結論:
- LSD1は,抑制性ヒストンマークを除去することによって,アンドロゲン受容体依存性遺伝子活性化において重要な役割を果たします.
- LSD1の活性を,例えばパルギリンで調節することは,前立腺がんのようなアンドロゲン受容体駆動性疾患に対する潜在的な治療戦略を提供します.
関連する概念動画
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X-chromosome...
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Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...


