Transition of LINE-1 DNA Methylation Status and Altered Expression in First and Third Trimester Placentas

被引:25
作者
He, Zhi-ming [1 ,2 ]
Li, Jinping [2 ,3 ,4 ,5 ]
Hwa, Yi Lisa [4 ,6 ]
Brost, Brian [3 ,4 ]
Fang, Qun [1 ]
Jiang, Shi-Wen [2 ,3 ,4 ,5 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Fetal Med Ctr, Dept Obstet & Gynecol, Guangzhou 510275, Guangdong, Peoples R China
[2] Mercer Univ, Sch Med, Dept Biol Sci, Savannah, GA USA
[3] Mayo Clin, Dept Obstet & Gynecol, Rochester, MN USA
[4] Mayo Coll Med, Rochester, MN USA
[5] Mem Hlth Univ, Med Ctr, Dept Obstet & Gynecol, Savannah, GA USA
[6] Mayo Clin, Dept Med, Rochester, MN USA
来源
PLOS ONE | 2014年 / 9卷 / 05期
关键词
CELL-PROLIFERATION; GENE-EXPRESSION; 5-METHYLCYTOSINE CONTENT; ENDOMETRIAL CANCERS; L1; RETROTRANSPOSONS; ELEMENTS; HYPOMETHYLATION; PREGNANCY; TISSUES; HYPERMETHYLATION;
D O I
10.1371/journal.pone.0096994
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DNA methylation plays a critical role in the regulation of gene expression, genomic DNA stability, cell proliferation, and malignant transformation. Common cellular features including fast tissue expansion, invasive growth, and active angiogenesis, have been noticed between placental development and tumorigenesis by many investigators. While the DNA hypomethylation and transcriptional activation of LINE-1 has been found to be a feature of tumorigenesis, it is not clear if similar changes could be involved in placental development. In this study, we assessed LINE-1 methylation in human placentas from different gestational ages and observed a significant decrease of LINE-1 methylation levels in third trimester placentas compared to first trimester placentas. Accompanying with this change is the significantly increased LINE-1 mRNA levels in third trimester placentas. Since no global DNA methylation change was detected between first and third trimesters, LINE-1 methylation changes appeared to be a specific epigenetic entity contributing to placental development. Indeed, further analyses showed that LINE-1 upregulation was correlated with higher levels of PCNA, suggesting a link between LINE-1 activation and fast proliferation of certain cellular components in third trimester placentas. Measurement of the DNMT1, DNMT3A, and DNMT3B expression found a significant reduction of DNMT3B between third and first trimesters, pointing to the possible involvement of this enzyme in the regulation of LINE-1 methylation. Taken together these results provided evidence for a dynamic temporal regulation of LINE-1 methylation and activation during placental development. These studies have laid a foundation for future investigation on the function of LINE-1 expression in human placenta under different patho-physiological conditions.
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页数:11
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