• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >A methyl-deficient diet modifies early B cell development
【24h】

A methyl-deficient diet modifies early B cell development

机译：甲基缺乏饮食会改变早期B细胞发育

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A functional methyl group donor is essential for the epigenetic regulation of all biological events due to the importance of DNA methylation and histone methylation as an epigenetic marker. However, the epigenetic alterations in the immune system due to methyl donor deficiency are not well known. In this study, we tried to address this question by studying the lymphocyte development and DNA methylation changes caused by a methyl-deficient diet (MDD). We fed one group of C57BL/6J mice with a methyl-sufficient diet (MSD) and the other group with an MDD for 5 months. Flow cytometry analyses of their immune systems showed a decrease in B220+ IgM+ (immature B) cells and an increase in B220+ IgM- (pro/pre-B) cells in the bone marrow of mice fed an MDD. By means of an in vitro OP9 coculture system, we recognized that this B220+ IgM- cell fraction from the MDD has an intrinsic developmental defect. When we quantitatively measured the mRNA expression levels of transcription factors and recombination machinery related to B cell development in the B220+ IgM- cell fraction of their bone marrow, we found that ADA, EBF1, DNTT and Pax5 mRNA expression levels were significantly downregulated in mice fed with an MDD. In addition, there was a drastic decrease in histone methylation profile H3K4me3 in the Pax5 and EBF1 promoters in these B220+ IgM- B cells. However, CpG-DNA methylation profiles had not changed and this revealed that these two promoters are demethylated even under an MSD condition. We also found changed expression levels of the Polycomb group genes (mel18, bmi1, Pc1, Pc2, Ring1A, Ring1B, Ph1) on semi-quantitative RT-PCR. These results indicate that under an MDD condition, early B cell development in bone marrow is easily affected by epigenetic alterations.
机译：由于DNA甲基化和组蛋白甲基化作为表观遗传标记的重要性，功能性甲基供体对于所有生物事件的表观遗传调控至关重要。然而，由于甲基供体缺乏而引起的免疫系统表观遗传学改变尚不为人所知。在这项研究中，我们试图通过研究由甲基缺乏饮食（MDD）引起的淋巴细胞发育和DNA甲基化变化来解决这个问题。我们给一组C57BL / 6J小鼠喂了甲基饮食（MSD），另一组给了MDD了5个月。流式细胞仪分析其免疫系统显示，喂食MDD的小鼠骨髓中B220 + IgM +（未成熟B）细胞减少，B220 + IgM-（pro / pre-B）细胞增加。通过体外OP9共培养系统，我们认识到来自MDD的B220 + IgM-细胞部分具有内在的发育缺陷。当我们定量测量骨髓中B220 + IgM-细胞部分中与B细胞发育相关的转录因子和重组机制的mRNA表达水平时，我们发现ADA，EBF1，DNTT和Pax5 mRNA表达水平在喂养小鼠中显着下调使用MDD。另外，在这些B220 + IgM-B细胞中，Pax5和EBF1启动子中的组蛋白甲基化谱H3K4me3急剧降低。但是，CpG-DNA甲基化谱图没有改变，这表明即使在MSD条件下，这两个启动子也已脱甲基。我们还发现半定量RT-PCR上Polycomb组基因（mel18，bmi1，Pc1，Pc2，Ring1A，Ring1B，Ph1）的表达水平已改变。这些结果表明在MDD条件下，骨髓中早期B细胞的发育很容易受到表观遗传改变的影响。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号