Dokuz Eylul University, Faculty of Medicine, Department of Pediatrics, Turkey.
Early Hum Dev. 2013 Mar;89(3):165-73. doi: 10.1016/j.earlhumdev.2012.09.016. Epub 2012 Oct 6.
DNA methylation and histone modifications are the most identified modifications that selectively activate or inactivate genes that control cell growth, proliferation, and apoptosis.
We hypothesized that alterations in gene expression due to hypoxic-ischemic brain damage was regulated by epigenetic mechanisms including DNA methylation and histone methylation.
To test this hypothesis, we established a rat model of HIE. Three groups were defined as hypoxic-ischemic, sham-operated, and control group.
The validity of the HIE model used in this study was confirmed by histological and immunohistochemical tests. Gene expressions related with apoptosis and angiogenesis were studied at 0.5, 3, 6 and 24h after HI or sham operation. DNA and histone methylation status was studied in the genes showing significant change in expression.
Most of the genes related with apoptosis and angiogenesis (Epo, Epor, Hif 1α, Hif3α, VEGFa, VEGFc, Casp1, Casp9, and Casp8ap2) induced early after HI (30min). All of these genes were unmethylated at the beginning of the insult and in the control group. DNA methylation percentage and histone methylation (H3K36) levels were not correlated with gen expression levels. To our knowledge this is the first study evaluating the role of epigenetic mechanisms in HIE model, therefore the absence of similar studies don't allow us to compare the present results. Further studies investigating different epigenetic mechanisms are needed.
DNA 甲基化和组蛋白修饰是最常见的修饰方式，它们可以选择性地激活或失活控制细胞生长、增殖和凋亡的基因。
我们假设由于缺氧缺血性脑损伤导致的基因表达改变是由表观遗传机制（包括 DNA 甲基化和组蛋白甲基化）调控的。
为了验证这一假设，我们建立了一个缺氧缺血性脑损伤大鼠模型。将三组定义为缺氧缺血组、假手术组和对照组。
大多数与凋亡和血管生成相关的基因（Epo、Epor、Hif1α、Hif3α、VEGFa、VEGFc、Casp1、Casp9 和 Casp8ap2）在 HI 或假手术后 0.5、3、6 和 24h 时诱导表达。这些与凋亡和血管生成相关的基因在 HI 后早期（30min）诱导表达。所有这些基因在损伤开始时和对照组中均未发生甲基化。DNA 甲基化百分比和组蛋白甲基化（H3K36）水平与基因表达水平无关。据我们所知，这是第一项评估表观遗传机制在缺氧缺血性脑损伤模型中作用的研究，因此缺乏类似的研究使我们无法比较目前的结果。需要进一步研究不同的表观遗传机制。
