...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Environmental Epigenetics >Bisphenol A-associated alterations in genome-wide DNA methylation and gene expression patterns reveal sequence-dependent and non-monotonic effects in human fetal liver
【24h】

Bisphenol A-associated alterations in genome-wide DNA methylation and gene expression patterns reveal sequence-dependent and non-monotonic effects in human fetal liver

机译：全基因组DNA甲基化和基因表达模式中双酚A的相关变化揭示了人类胎儿肝脏中的序列依赖性和非单调效应

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Bisphenol A (BPA), a high production volume chemical widely used in consumer products, is an endocrine active compound associated with complex epigenetic responses in animal models and humans. Developmental BPA exposure in mice previously revealed widespread changes in the mouse liver methylome. Here, we undertake the first epigenome-wide analysis of the effect of BPA concentration on human fetal liver DNA methylation. Enzymatic enrichment of genomic DNA for high CG density and methylation followed by next-generation sequencing yielded data for positional methylation across the genome. Comparing three groups of BPA-exposed subjects ( n ?=?18; 6 per group), high (35.44–96.76?ng/g), low (3.50 to 5.79?ng/g), and non-detect (0.83?ng/g), revealed regions of altered methylation. Similar numbers of regions of altered methylations were detected in pairwise comparisons; however, their genomic locations were distinct between the non-detect and low or high BPA groups. In general, BPA levels were positively associated with methylation in CpG islands and negatively associated with methylation in CpG shores, shelves, and repetitive regions. DNA methylation at the SNORD imprinted cluster (15q11q13) illustrated both linear and non-monotonic associations with BPA levels. Integrated methylation and RNA-sequencing gene expression analysis revealed differential regulation of transcription at low BPA levels, as well as expression changes in RNA for ligand-binding proteins as BPA levels increase. BPA levels in human fetal liver tissue are associated with complex linear and non-monotonic as well as sequence-dependent alterations in DNA methylation. Future longitudinal studies are needed to link these changes with altered health risks.
机译：双酚A（BPA）是一种高产量的化学物质，广泛用于消费品中，是一种内分泌活性化合物，与动物模型和人类的复杂表观遗传反应相关。小鼠中发育性BPA暴露先前揭示了小鼠肝脏甲基化组的广泛变化。在这里，我们进行了BPA浓度对人胎肝DNA甲基化影响的第一个表观基因组分析。高CG密度和甲基化的酶富集基因组DNA，然后进行下一代测序，得到了整个基因组中位置甲基化的数据。比较三组接触BPA的受试者（n = 18，每组6个），高（35.44-96.76 ng / g），低（3.50至5.79 ng / g）和未检出（<0.83？ ng / g），发现甲基化区域发生了变化。在成对比较中检测到相似数目的甲基化改变区域;然而，它们的基因组位置在未检出和低或高BPA组之间是不同的。通常，BPA水平与CpG岛中的甲基化呈正相关，而与CpG海岸，大陆架和重复性区域中的甲基化呈负相关。在SNORD印迹簇（15q11q13）处的DNA甲基化说明了BPA水平与线性和非单调关联。集成的甲基化和RNA测序基因表达分析表明，在低BPA水平下转录的差异调节以及随着BPA水平增加配体结合蛋白的RNA表达变化。人胎儿肝脏组织中的BPA水平与DNA甲基化中复杂的线性和非单调以及序列依赖性变化有关。需要未来的纵向研究来将这些变化与改变的健康风险联系起来。

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