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标识,表征和鼠类转基因位基因的遗传性:对非遗传的影响
Anastasiya Kazachenka1, Tessa M Bertozzi1, Marcela K Sjoberg-Herrera2
1Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
Cell
|November 21, 2018
概括
逆转移子,像内A粒子 (IAP) 元素一样,在小鼠中显示可变的DNA甲基化,影响基因表达和外颜色. 这些表观遗传状态在受精后被重置,但在下一代被重新建立.
科学领域:
- 表观遗传学
- 基因组学
- 发育生物学
背景情况:
- 包括内A粒子 (IAP) 元素在内的逆转移子构成了小鼠基因组的重要组成部分.
- 表观遗传机制通常会抑制逆转移素的活性.
- 在基因相同的个体中,Agouti可行的黄色 (Avy) 位点表现出可变的DNA甲基化,导致跨代遗传的可变的外套颜色表达.
研究的目的:
- 识别具有与Avy位置相似的表观遗传性质的小鼠内A粒子 (IAP) 元素.
- 研究这些已识别的IAP的表观遗传行为和调节潜力.
- 检查跨代IAP可变甲基化状态的遗传模式和重编程.
主要方法:
- 对C57BL/6J小鼠进行全基因组查,以确定具有可变表观遗传状态的IAP.
- 在特定的IAP位点进行DNA甲基化分析.
- 评估IAP作为邻近基因的促进剂的作用.
- 在受精后和跨代 IAP 甲基化重编程的分析.
主要成果:
- 多个C57BL/6J小鼠IAP被确定具有可变的DNA甲基化,类似于Avy位点.
- 每个IAP在个体内保持稳定的甲基化状态,但在个体之间有所不同.
- 这些IAP很少作为邻近基因的促进剂,它们的甲基化是局部特异性的.
- 对于CTCF结合点,可变甲基化IAP的旁边区域进行了丰富.
- 在受精后重新编程了可变的IAP甲基化状态,并在随后的世代中重新建立.
结论:
- 在小鼠基因组中,可变甲基化的IAP是常见的,并表现出特定于位置的表观遗传调节.
- 在IAP中重新编程和重新建立稳定表观遗传状态挑战了非遗传遗传模型的普遍性.
- 这些发现突显了逆转移体的动态表观遗传性质以及它们在产生表型变异中的作用.
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