摘要
长点缀核苷酸元-1(LINE-1)的表观遗传调控反转录转座事件在早期的发展中起着至关重要的作用。我们发现,在神经组织中LINE-1的甲基化与神经管缺陷(NTD)发病机制相关。在此,我们进一步评估来自死产的被忽视的热带病胎儿组织中三个胚芽层的人LINE-1(L1Hs)甲基化,以定义组织特异性甲基化和位点特异性非甲基化在L1Hs启动子区的CpG位点内的模式。稳定、组织特异性L1Hs甲基化模式在三个胎儿的胚芽层谱系,胎盘和孕妇外周血全部进行了观察。来自孕妇外周血的样品表现出的L1Hs甲基化水平最高(64.95%),来自胎盘的样品甲基化水平最低(26.82%)。来自神经管缺陷组和对照组的样品中,仅在被NTD影响的脑组织L1Hs甲基化降低(7.35%)是具有意义的,尤其是女性(8.98%)。神经管缺陷组中L1Hs低甲基化还与L1Hs编码转录物的与表达水平的显著增加相关(r = -0.846,P = 0.004)。这可能是由于L1Hs异常低甲基化导致染色质亲和性基因组DNA的不稳定和变化,如这项研究中显示的用甲基化抑制剂5-Aza处理HCT-15细胞。
关键词: DNA甲基化,人长点缀核苷酸元-1,基因不稳定性,神经管缺陷,逆转录转座
Current Molecular Medicine
Title:Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects
Volume: 15 Issue: 5
Author(s): L. Wang, S. Chang, J. Guan, S. Shangguan, X. Lu, Z. Wang, L. Wu, J. Zou, H. Zhao, Y. Bao, Z. Qiu, B. Niu and T. Zhang
Affiliation:
关键词: DNA甲基化,人长点缀核苷酸元-1,基因不稳定性,神经管缺陷,逆转录转座
摘要: Epigenetic regulation of long interspersed nucleotide element-1 (LINE-1) retrotransposition events plays crucial roles during early development. Previously we showed that LINE-1 hypomethylation in neuronal tissues is associated with pathogenesis of neural tube defect (NTD). Herein, we further evaluated LINE-1 Homo sapiens (L1Hs) methylation in tissues derived from three germ layers of stillborn NTD fetuses, to define patterns of tissuespecific methylation and site-specific hypomethylation at CpG sites within an L1Hs promoter region. Stable, tissue-specific L1Hs methylation patterns throughout three germ layer lineages of the fetus, placenta, and maternal peripheral blood were observed. Samples from maternal peripheral blood exhibited the highest level of L1Hs methylation (64.95%) and that from placenta showed the lowest (26.82%). Between samples from NTDs and controls, decrease in L1Hs methylation was only significant in NTD-affected brain tissue at 7.35%, especially in females (8.98%). L1Hs hypomethylation in NTDs was also associated with a significant increase in expression level of an L1Hs-encoded transcript in females (r = -0.846, p = 0.004). This could be due to genomic DNA instability and alternation in chromatins accessibility resulted from abnormal L1Hs hypomethylation, as showed in this study with HCT-15 cells treated with methylation inhibitor 5-Aza.
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L. Wang, S. Chang, J. Guan, S. Shangguan, X. Lu, Z. Wang, L. Wu, J. Zou, H. Zhao, Y. Bao, Z. Qiu, B. Niu and T. Zhang , Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects, Current Molecular Medicine 2015; 15 (5) . https://dx.doi.org/10.2174/1566524015666150630130229
DOI https://dx.doi.org/10.2174/1566524015666150630130229 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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