基因间和内含子 DNA 低甲基化区域作为印迹域的潜在调节因子。
Intergenic and intronic DNA hypomethylated regions as putative regulators of imprinted domains.
机构信息
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
出版信息
Epigenomics. 2018 Apr 1;10(4):445-461. doi: 10.2217/epi-2017-0125. Epub 2018 Mar 23.
Abstract
AIM
To investigate the regulatory potential of intergenic/intronic hypomethylated regions (iHMRs) within imprinted domains.
MATERIALS & METHODS: Based on the preliminary results of the histone modification and conservation profiles, we conducted reporter assays on the Peg3 and H19 domain iHMRs. The in vitro results were confirmed by the in vivo deletion of Peg3-iHMR designed to test its function in the Peg3 imprinted domain.
RESULTS & CONCLUSION: Initial bioinformatic analyses suggested that some iHMRs may be noncanonical enhancers for imprinted genes. Consistent with this, Peg3- and H19-iHMRs showed context-dependent promoter and enhancer activity. Further, deletion of Peg3-iHMR resulted in allele- and sex-specific misregulation of several imprinted genes within the domain. Taken together, these results suggest that some iHMRs may function as domain-wide regulators for the associated imprinted domains.
摘要
目的
研究印迹域内基因间/内含子低甲基化区域（iHMRs）的调控潜能。
材料与方法
根据组蛋白修饰和保守性分析的初步结果，我们针对 Peg3 和 H19 结构域的 iHMR 进行了报告基因检测。通过 Peg3-iHMR 的体外缺失实验，证实了其在 Peg3 印迹域中功能的体内实验结果。
结果与结论
初步的生物信息学分析表明，一些 iHMR 可能是非典型的印迹基因增强子。与这一观点一致的是，Peg3 和 H19-iHMR 表现出依赖于上下文的启动子和增强子活性。此外，Peg3-iHMR 的缺失导致该结构域内多个印迹基因出现等位基因和性别特异性的失调。综上所述，这些结果表明，一些 iHMR 可能作为相关印迹域的全域调控因子发挥作用。
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