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:
Keywords:
DNA methylation, LINE-1 homo sapiens (L1Hs), genomic instability, Neural tube defects (NTDs),
retrotransposition.
Abstract: 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.
