Genome-wide analysis of epigenomic alterations in fetal mouse forebrain after exposure to low doses of bisphenol A.
Genome-wide analysis of epigenomic alterations in fetal mouse forebrain after exposure to low doses of bisphenol A.
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DOI：
10.1016/j.bbrc.2008.09.028
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发表时间：
2008-11
影响因子：
3.1
通讯作者：
T. Yaoi;K. Itoh;Keiko Nakamura;H. Ogi;Yasuhiro Fujiwara;S. Fushiki
中科院分区：
文献类型：
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作者：
T. Yaoi;K. Itoh;Keiko Nakamura;H. Ogi;Yasuhiro Fujiwara;S. Fushiki
双酚A（BPA）是一种内分泌干扰物，广泛分布于环境中。我们一直在研究低剂量BPA对小鼠前脑发育的影响。在这里，我们研究了在E12.5和E14.5时母体暴露于BPA对小鼠前脑表观基因组的全基因组效应。我们扫描了2500个Not I位点的CpG甲基化状态，代表48个（去）甲基化的独特位点。甲基化状态在大多数是主要发育阶段依赖。几乎所有克隆的Not I基因座均位于转录单位5′端附近的CpG岛（CGI）上。两个功能相关基因的mRNA表达随着发育和BPA暴露而变化。在这两个基因中，转录水平的变化与Not I甲基化状态的变化密切相关。总之，暴露于BPA后启动子相关CGIs的表观遗传学改变可能是对大脑发育的一些影响的基础。
Bisphenol A (BPA) is one of endocrine disrupting chemicals, being distributed widely in the environment. We have been studying the low dose effects of BPA on murine forebrain development. Here, we have investigated the genome-wide effect of maternal exposure to BPA on the epigenome in mouse forebrain at E12.5 and at E14.5. We scanned CpG methylation status in 2500 Not I loci, representing 48 (de)methylated unique loci. Methylation status in most of them was primarily developmental stage-dependent. Each of almost all cloned Not I loci was located in a CpG island (CGI) adjacent to 5′ end of the transcriptional unit. The mRNA expression of two functionally related genes changed with development as well as the exposure to BPA. In both genes, changes at the transcriptional level correlated well with the changes in Not I methylation status. Taken together, epigenetic alterations in promoter-associated CGIs after exposure to BPA may underlie some effects on brain development.