title: Abnormal epigenetic regulation of the gene expression levels of Wnt2b and Wnt7b: Implications for neural tube defects.
abstract: The association between Wnt genes and neural tube defects (NTDs) is recognized, however, it remains to be fully elucidated. Our previous study demonstrated that epigenetic mechanisms are affected in human NTDs. Therefore, the present study aimed to evaluate whether Wnt2b and Wnt7b are susceptible to abnormal epigenetic modification in NTDs, using chromatin immunoprecipitation assays to evaluate histone enrichments and the MassARRAY platform to detect the methylation levels of target regions within Wnt genes. The results demonstrated that the transcriptional activities of Wnt2b and Wnt7b were abnormally upregulated in mouse fetuses with NTDs and, in the GC‑rich promoters of these genes, histone 3 lysine 4 (H3K4) acetylation was enriched, whereas H3K27 trimethylation was reduced. Furthermore, several CpG sites in the altered histone modification of target regions were significantly hypomethylated. The present study also detected abnormal epigenetic modifications of these Wnt genes in human NTDs. In conclusion, the present study detected abnormal upregulation in the levels of Wnt2b and Wnt7b, and hypothesized that the alterations may be due to the ectopic opening of chromatin structure. These results improve understanding of the dysregulation of epigenetic modification of Wnt genes in NTDs.
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, P.R. China.
authors.forename: Baoling
authors.initials: B
authors.lastname: Bai
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, P.R. China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, P.R. China.
authors.forename: Huili
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000235:genetics; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009436:Neural Tube Defects / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016135:Spinal Dysraphism / Q000235:genetics; D014212:Tretinoin; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D006657:Histones; D011518:Proto-Oncogene Proteins; C115496:WNT2B protein, human; C490675:WNT7B protein, human; D051153:Wnt Proteins; C492031:Wnt2b protein, mouse; C095937:Wnt7b protein, mouse; D014212:Tretinoin