Dot1p通过核细胞核核的甲基化来调节酵母中的沉默
Fred van Leeuwen1, Philip R Gafken, Daniel E Gottschling
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Cell
|June 28, 2002
概括
Dot1蛋白质甲基化素H3素79,一个关键的表观遗传标记. 这种甲基化对于保持染色质中的基因沉默至关重要,影响酵母中的端粒沉默.
科学领域:
- 表观遗传学和分子生物学
- 染色体生物学 染色体生物学
- 酵母遗传学 酵母遗传学
背景情况:
- 在Saccharomyces cerevisiae (酵母菌) 中,端粒沉默是一种经过充分研究的现象.
- DOT1基因最初因其在这种沉默过程中的作用而被确定.
- 基因组蛋白修饰是基因表达和染色质结构的关键调节者.
研究的目的:
- 为了阐明DOT1基因产物的分子功能,Dot1p.
- 为了识别Dot1p催化的特定的组素修饰.
- 了解这种修饰在端粒沉默和染色体调节中的作用.
主要方法:
- 生物化学测试以确定Dot1p酶活性.
- 染色体免疫沉 (ChIP) 来评估蛋白质局部化.
- 对野生型和dot1delta酵母菌株的基因沉默和蛋白质分布的分析.
主要成果:
- 发现Dot1p在lysine 79 (H3K79甲基化) 上特异地甲基化组织蛋白H3.
- 这种甲基化发生在组装的染色质的背景下.
- Dot1p是负责H3K79体内甲基化的主要酶,影响大约90%的基因素H3.
- Dot1p功能的丧失 (dot1delta) 损害了沉默,并改变了沉默蛋白的分布.
结论:
- 通过Dot1p进行的Histon H3 lysine 79甲基化对于适当的端粒沉默是必不可少的.
- H3K79甲基化可能通过防止沉默蛋白 (如Sir蛋白) 与其他基因组区域结合,将沉默限制在特定的位置.
- Dot1p和基因组H3的保存性表明,类似的表观遗传调节机制在其他真核生物中也存在.
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