Increased DNA replication length offsets developmental defects induced by hypomorphic DNA methylcytosine methyltransferase activity [RNA-Seq]. Increased DNA replication length offsets developmental defects induced by hypomorphic DNA methylcytosine methyltransferase activity [RNA-Seq]

Dnmt1 is a key methyltransferase involved in the maintenance of DNA methylation. To determine whether developmental defects induced by hypomorphic DNA 5-methylcytosine methyltransferase activity can be offset by increasing DNA replication time, we produced fish that were mutant for both dnmt1 and DNA polymerase epsilon (pole1) and compared their whole genome bisultite sequencing and gene expression profiles to WT ones. We further determine that the observed rescue effect by pole1 is specific to dnmt1 by comparing whole-genome bisulfite sequencing and gene expression profiles of mutants for the Methionine Adenosyltransferase 2A (mat2aa) and microchromosome 10 (mcm10) Overall design: Characterisation of gene expression profiles of dnmt1/pole1 single or double mutant fish, mat2a/pole1 single or double mutant fish or mcm10 single mutant fish via RNA-Seq

DNA甲基转移酶1（Dnmt1）是参与维持DNA甲基化的关键甲基转移酶。为明确活性降低的DNA 5-甲基胞嘧啶甲基转移酶活性所诱导的发育缺陷是否可通过延长DNA复制时间予以弥补，我们构建了同时携带dnmt1与DNA聚合酶ε（pole1）突变的鱼类，并将其全基因组亚硫酸氢盐测序结果与基因表达谱与野生型（WT）样本进行对比。我们进一步通过比对甲硫氨酸腺苷转移酶2A（Methionine Adenosyltransferase 2A，mat2aa）突变体与微染色体10（mcm10）突变体的全基因组亚硫酸氢盐测序及基因表达谱，证实了pole1所介导的挽救效应对dnmt1具有特异性。整体实验设计：通过RNA测序（RNA-Seq），对dnmt1/pole1单突变或双突变鱼类、mat2a/pole1单突变或双突变鱼类，以及mcm10单突变鱼类的基因表达谱进行表征。