title: Spina bifida in fetus is associated with an altered pattern of DNA methylation in placenta.
abstract: Failure in closure of neural tube leads to neural tube defects (NTDs), which are among the most common symptoms of human birth defects. Although epigenetic status in placenta is linked to fetal development, the mechanism behind this remains unknown. Because of the importance of DNA methylation in gene function, we set to explore whether or not DNA methylation in human placenta is also linked to fetal NTDs. Here we show for the first time that alteration of DNA methylation in placenta is closely associated with the phenotypes of fetal spina bifida (Sb). We found that patterns of DNA methylation for genes in neurological system process were differentially altered in the Sb placenta. In particular, the transcription regulatory regions of TRIM26 and GANS were kept at the hypomethylation status in Sb placenta alone. Accordingly, the protein levels of TRIM26 and GNAS were significantly elevated only in the Sb placenta but not in the Sb-affected fetuses. In cellular model of CHO cells deficient in Dihydrofolate reductase and treated with 5-aza-2'-deoxycytidine, the protein levels of GNAS and TRIM26 were significantly higher than those in normal control cells. These findings suggested that epigenetic status of genes in placenta have profound impacts on the development of NTDs.
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|Laboratory of Molecular Biology, Zhengzhou Normal University, Zhengzhou, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: WHO Collaborating Center for Research in Reproductive Health and Population Science, Institute of Population Research, Peking University, Beijing, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Pei
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|Laboratory of Molecular Biology, Zhengzhou Normal University, Zhengzhou, China.
authors.forename: Runting
authors.initials: R
authors.lastname: Li
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Graduate University of the Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|Graduate University of the Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|Graduate University of the Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Tan
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Graduate University of the Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jingdong J
authors.initials: JJ
authors.lastname: Han
authors.affiliation: WHO Collaborating Center for Research in Reproductive Health and Population Science, Institute of Population Research, Peking University, Beijing, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|Laboratory of Molecular Biology, Zhengzhou Normal University, Zhengzhou, China.|Graduate University of the Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Runlin Z
authors.initials: RZ
authors.lastname: Ma
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D016135:Spinal Dysraphism / Q000235:genetics / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D000070584:Tripartite Motif Proteins; C519439:TRIM26 protein, human; D044767:Ubiquitin-Protein Ligases