代位基因组是胚胎DNA甲基化重编程的基础
Patrick J Murphy1, Shan Fu Wu1, Cody R James1
1Howard Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Cell
|February 20, 2018
概括
在斑马鱼胚胎中,含有基因组H2A变异H2A.Z(FV) 和H3K4me1的取位核子会阻止DNA甲基化. 这种表观遗传机制控制了早期发育和遗传过程中的基因激活或抑制.
科学领域:
- 发育生物学
- 表观遗传学
- 基因组学
背景情况:
- 表观遗传标记指导从生殖线到胚胎的转变,影响干细胞编程和遗传.
- 在斑马鱼中,DNA甲基化在静止胚胎中建立,保持父模式和母模式重新编程.
- 了解控制这些表观遗传变化的机制对于发育生物学至关重要.
研究的目的:
- 阐明斑马鱼从生殖线到胚胎过渡期间编程DNA甲基化模式的机制.
- 确定特定核体在调节DNA甲基化和基因表达中的作用.
- 调查干扰这些表观遗传标记的后果.
主要方法:
- 染色体免疫沉 (ChIP) 来确定核细胞占用率和基因组修饰.
- 用于评估全基因组甲基化模式的DNA甲基化分析.
- 功能性测试用于研究核体扰动对基因表达和DNA甲基化的影响.
主要成果:
- 含有H2A.Z (FV) 和H3K4me1的"取代者"核细胞占据精子和分裂胚胎中的DNA无甲基化区域.
- 这些核细胞体在家庭管理和早期胚胎基因的促进者中被发现.
- 取位基因的丧失导致DNA甲基化积累,而其增加导致低甲基化和异常基因激活.
结论:
- 在静止发育阶段,取位核酶能积极抑制DNA甲基化.
- 这种机制在转录开始时平衡父母基因的激活或抑制.
- 在斑马鱼的早期发育过程中,占位核体是表观遗传重编程和基因表达的关键调节者.
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