title: Transition of LINE-1 DNA methylation status and altered expression in first and third trimester placentas.
abstract: 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.
authors.affiliation: Fetal Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China; Department of Biological Science, Mercer University School of Medicine, Savannah, Georgia, United States of America.
authors.forename: Zhi-ming
authors.initials: ZM
authors.lastname: He
authors.affiliation: Department of Biological Science, Mercer University School of Medicine, Savannah, Georgia, United States of America; Department of Obstetrics and Gynecology, Mayo Clinic and Mayo College of Medicine, Rochester, Minnesota, United States of America; Department of Obstetrics and Gynecology, Memorial Health University Medical Center, Savannah, Georgia, United States of America.
authors.forename: Jinping
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medicine, Mayo Clinic and Mayo College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Yi Lisa
authors.initials: YL
authors.lastname: Hwa
authors.affiliation: Department of Obstetrics and Gynecology, Mayo Clinic and Mayo College of Medicine, Rochester, Minnesota, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Brost
authors.affiliation: Fetal Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Department of Biological Science, Mercer University School of Medicine, Savannah, Georgia, United States of America; Department of Obstetrics and Gynecology, Mayo Clinic and Mayo College of Medicine, Rochester, Minnesota, United States of America; Department of Obstetrics and Gynecology, Memorial Health University Medical Center, Savannah, Georgia, United States of America.
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Jiang
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008969:Molecular Sequence Data; D009035:Mothers; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics; D011261:Pregnancy Trimester, First / Q000235:genetics*; D011263:Pregnancy Trimester, Third / Q000235:genetics*; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases