通过Drosophila表观遗传转录调节器Ash1的希斯甲基化
Christian Beisel1, Axel Imhof, Jaime Greene
1Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
Nature
|October 25, 2002
概括
表观遗传激活剂Ash1是一种基因素甲基转移酶,通过甲基化基因素建立活跃的转录模式. 这种甲基化招募了染色质重塑剂,促进了细胞的确定和功能.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 基因规则 基因规则
背景情况:
- 稳定的表观遗传转录模式对于细胞的确定和功能至关重要.
- 表观遗传调节涉及激活剂,抑制剂和不太了解的信号,如染色质结构和基因素修饰.
- 基因组甲基化是影响基因表达的关键表观遗传机制.
研究的目的:
- 调查表观遗传激活剂Ash1在建立转录模式中的作用.
- 确定Ash1是否作为基因组甲基转移酶 (HMTase) 起作用,并确定其标残留物.
- 阐明Ash1介导的组素甲基化影响染色质结构和基因激活的机制.
主要方法:
- 生物化学分析以描述Ash1作为一个多催化HMTase.
- 对基因甲基化模式 (H3K4,H3K9,H4K20) 在基因促进体的分析.
- 在Drosophila中染色体免疫沉 (ChIP) 评估Ash1和Brahma (Brm) 招募.
- 抑制研究评估表观遗传抑制剂与染色素的相互作用.
主要成果:
- Ash1被确定为一种甲基化H3K4,H3K9和H4K20的HMTase.
- Ash1的转录激活与这些特定的氨酸残留在基因促进体中的甲基化相关.
- 灰1介导的甲基化作为布拉玛 (Brm) 染色质重塑复合物的结合点.
- Ash1甲基化抑制了表观遗传抑制剂与染色质的相互作用.
- 在Drosophila中Ultrabithorax转录的表观遗传激活涉及Ash1甲基化和Brm招募.
结论:
- 由Ash1进行的基因组胺甲基化是建立活跃表观遗传转录模式的关键信号.
- Ash1介导的组素甲基化通过招募染色质重塑剂,在细胞确定和功能中发挥关键作用.
- 这些发现提供了基因组甲基化和由表观遗传激活剂调节基因表达之间的机制联系.
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