对H2A.Z的竞争是重复元素去压制的发展影响的基础
Fanju W Meng1, Kristin E Murphy1, Claire E Makowski1
1University of Rochester Medical Center, Rochester, NY 14642, USA.
概括
基因组突变H2A.Z在发育早期调节基因转录. 它的水平影响胚胎对重复元素的敏感性,揭示了对表观遗传因素的竞争,并影响了转录输出.
科学领域:
- 表观遗传学和发育生物学
- 染色体生物学 染色体生物学
- 基因组学就是基因组学.
背景情况:
- 基因组突变H2A.Z对于早期胚胎发育和转录调节至关重要.
- H2A.Z控制了促进剂和增强剂的基因表达.
- 了解H2A.Z的动态是解读发育过程的关键.
研究的目的:
- 研究H2A.Z在斑马鱼早期发育过程中的重复元素中的作用.
- 为了确定H2A.Z水平如何影响转录输出,以应对重复的元素活动.
- 阐明重复元素和H2A.Z相互作用以影响基因表达的机制.
主要方法:
- 染色体免疫沉 (ChIP) 测定用于映射H2A.Z和H3K9me3.3.
- 使用像ATAC-seq.这样的技术分析染色质可访问性的分析.
- 通过RNA测序进行基因表达分析.
- 斑马鱼转基因对于H2A.Z过度表达.
主要成果:
- 在斑马鱼早期发育过程中,在年轻的重复元素 (转子体,LINE,LTR) 中发现了H2A.Z.
- 重复的元素激活与增加的H2A.Z,减少的H3K9me3和增加的染色质可访问性相关.
- 重复元素的去抑制导致基因位置的H2A.Z损失,导致相邻的基因沉默.
- 过度表达H2A.Z可以减轻重复元素去压的沉默效应.
结论:
- 胚胎对重复元素去抑制的敏感性是由H2A.Z蛋白水平决定的.
- 重复的元素可以作为核沉器的表观遗传因素,如H2A.Z. .
- 对H2A.Z的竞争对整体发育转录输出有重大影响.
- 重复元素和H2A.Z之间的相互作用突出了发展表型的基础的反作用生物过程.
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