title: Genome-Wide Mapping of 5mC and 5hmC Identified Differentially Modified Genomic Regions in Late-Onset Severe Preeclampsia: A Pilot Study.
abstract: Preeclampsia (PE) is a leading cause of perinatal morbidity and mortality. However, as a common form of PE, the etiology of late-onset PE is elusive. We analyzed 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in the placentas of late-onset severe PE patients (n = 4) and normal controls (n = 4) using a (hydroxy)methylated DNA immunoprecipitation approach combined with deep sequencing ([h]MeDIP-seq), and the results were verified by (h)MeDIP-qPCR. The most significant differentially methylated regions (DMRs) were verified by MassARRAY EppiTYPER in an enlarged sample size (n = 20). Bioinformatics analysis identified 714 peaks of 5mC that were associated with 403 genes and 119 peaks of 5hmC that were associated with 61 genes, thus showing significant differences between the PE patients and the controls (>2-fold, p<0.05). Further, only one gene, PTPRN2, had both 5mC and 5hmC changes in patients. The ErbB signaling pathway was enriched in those 403 genes that had significantly different 5mC level between the groups. This genome-wide mapping of 5mC and 5hmC in late-onset severe PE and normal controls demonstrates that both 5mC and 5hmC play epigenetic roles in the regulation of the disease, but work independently. We reveal the genome-wide mapping of DNA methylation and DNA hydroxymethylation in late-onset PE placentas for the first time, and the identified ErbB signaling pathway and the gene PTPRN2 may be relevant to the epigenetic pathogenesis of late-onset PE.
authors.affiliation: Obstetrics Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China, 200011.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Epigenetics of Shanghai Ministry of Education, School of Basic Medicine and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: Ruitu
authors.initials: R
authors.lastname: Lv
authors.affiliation: Key Laboratory of Epigenetics of Shanghai Ministry of Education, School of Basic Medicine and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
authors.forename: Lingchun
authors.initials: L
authors.lastname: Kong
authors.affiliation: Obstetrics Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China, 200011.
authors.forename: Haidong
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Epigenetics of Shanghai Ministry of Education, School of Basic Medicine and Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China; Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Lan
authors.affiliation: Obstetrics Department, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China, 200011.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Li
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism* / Q000031:analogs & derivatives; D000328:Adult; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D010865:Pilot Projects; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; C512478:EGFR protein, human; D066246:ErbB Receptors; C102889:PTPRN2 protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8