A role for DNA methylation in gastrulation and somite patterning
A role for DNA methylation in gastrulation and somite patterning
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DOI：
10.1006/dbio.1998.9105
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发表时间：
1999-02-15
影响因子：
2.7
通讯作者：
Ekker, M
中科院分区：
文献类型：
--
作者：
Martin, CC;Laforest, L;Ekker, M
DNA甲基化是控制遗传信息的重要表观遗传因素。在这项研究中，我们分析了DNA甲基转移酶基因的表达，并研究了斑马鱼早期发育过程中的DNA甲基化模式。斑马鱼DNA甲基转移酶基因（MTase）的母体转录本普遍存在于早期胚胎中，在囊胚期后总体水平下降。在24小时，甲基转移酶mRNA主要存在于脑、神经管、眼和分化体节中。MTase在体节中的表达在体节的前细胞中最高。尽管高水平的MTase mRNA在囊胚期胚胎，我们观察到DNA低甲基化在囊胚和原肠胚阶段相比，精子或较老的胚胎。用5-氮杂胞苷（5-azaC）和5-氮杂-2-脱氧胞苷（5-azadC）（已知在哺乳动物细胞中诱导细胞分化和DNA低甲基化的核苷酸类似物）处理的斑马鱼胚胎表现出DNA低甲基化和发育扰动。这些缺陷特别是在囊胚期开始时，就在囊胚中期过渡之前处理的胚胎中观察到的。最常见的表型是尾部的缺失和体节的异常模式。头部发育在一些胚胎中也会受到影响。组织学和原位杂交分析显示，在处理的胚胎分化脊索和中线肌肉的全部或部分损失。当在原肠胚形成过程中检查时，5-azaC处理的胚胎具有缩短和增厚的轴向中胚层，我们提出DNA甲基化是正常原肠胚形成和随后的背侧中胚层图案化所必需的。(C)北京：科学出版社.
DNA methylation constitutes an important epigenetic factor in the control of genetic information. In this study, we analyzed expression of the DNA methyltransferase gene and examined DNA methylation patterns during early development of the zebrafish. Maternal transcripts of the zebrafish DNA methyltransferase gene (MTase) are ubiquitously present at high levels in early embryos with overall levels decreasing after the blastula stage. At 24 h, methyltransferase mRNA is predominantly found in the brain, neural tube, eyes, and differentiating somites. Expression of MTase in the somites is highest in the anterior cells of the somites. Despite the high levels of MTase mRNA in blastula-stage embryos, we observe DNA hypomethylation at the blastula and gastrula stages compared to sperm or older embryos. Zebrafish embryos treated with 5-azacytidine (5-azaC) and 5-aza-2-deoxycytidine (5-azadC), nucleotide analogs known to induce cellular differentiation and DNA hypomethylation in mammalian cells, exhibit DNA hypomethylation and developmental perturbations. These defects are specifically observed in embryos treated at the beginning of the blastula period, just prior to midblastula transition. The most common phenotype is the loss of tail and abnormal patterning of somites. Head development is also affected in some embryos. Histological and in situ hybridization analyses reveal whole or partial loss of a differentiated notochord and midline muscle in treated embryos. When examined during gastrulation, 5-azaC-treated embryos have a shortened and thickened axial mesoderm, We propose that DNA methylation is required for normal gastrulation and subsequent patterning of the dorsal mesoderm. (C) 1999 Academic Press.