LSD1去甲基抑制的组素标记,以促进雄激素受体依赖转录
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
概括
氨酸特异性去甲基酶1 (LSD1) 与雄激素受体相互作用,激活前列腺细胞中的基因转录和细胞增殖. 用帕基林抑制LSD1阻断了这些效应,提供了一种新的治疗策略.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 细胞中的基因调节涉及染色质修饰剂和转录因子,如雄激素受体.
- 在特定的氨酸残留物中,素甲基化状态调节了基因激活和抑制.
研究的目的:
- 调查氨酸特异性脱甲酶1 (LSD1) 在前列腺细胞中雄激素受体介导基因调节中的作用.
- 为了确定LSD1活动是否可以调节以控制雄激素受体功能.
主要方法:
- 在前列腺组织中对LSD1和雄激素受体的同局部化研究.
- 在体外和体内相互作用测定.
- 与雄激素受体依赖的转录分析.
- 染色体免疫沉 (ChIP) 分析.
- 关于LSD1.1的淘汰研究.
- 使用帕基林抑制LSD1.
主要成果:
- 在正常和瘤前列腺细胞中,LSD1与雄激素受体共同定位并与其相互作用.
- LSD1刺激了依赖于雄激素受体的转录和细胞增殖.
- 敲除LSD1取消了雄激素诱导的转录激活和扩散.
- LSD1与雄激素受体形成联体依赖的染色质复合体.
- 在lysine 9 (H3-K9) 处LSD1去甲基化组织基因H3,缓解抑制标记和去抑制基因.
- 帕基林抑制了LSD1的活性,阻断了H3-K9脱甲基化和依赖于雄激素受体的转录.
结论:
- LSD1通过去除压制性基因素标记,在依赖雄激素受体的基因激活中起着至关重要的作用.
- 调节LSD1活性,例如用帕基林,为像前列腺癌这样的雄激素受体驱动疾病提供了潜在的治疗策略.
相关概念视频
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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
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