title: Gene expression of epigenetic regulatory factors related to primary silencing mechanism is less susceptible to lower doses of bisphenol A in embryonic hypothalamic cells.
abstract: DNA methyltransferases (DNMTs) are associated with epigenetic regulation of gene expression, and methyl-CpG binding protein 2 (MECP2) acts as a long-range regulator of methylated genes. We evaluated the effects of bisphenol A (BPA) on embryonic mouse hypothalamic cells, with particular emphasis on the gene expression of Dnmts (Dnmt1, Dnmt3a, and Dnmt3b) and Mecp2 isoforms. In a dose-dependent (0.02-200 µM BPA) 3-hr experiment, real-time reverse transcription polymerase chain reaction revealed that gene expression of both Dnmts and Mecp2_e2 was affected at 200 µM and that of Mecp2_e1 was affected at > 20 µM. These results suggest that gene expression of Dnmts and Mecp2 are less susceptible to lower doses of BPA in developing hypothalamic cells. However, as BPA concentration increases, this agent has the potential to alter gene expression of key players that provide stability and flexibility of epigenetic gene regulation, which could disrupt the normal development of hypothalamic functions.
authors.affiliation: Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University, Kagawa, Japan. warita@med.kagawa-u-ac.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Warita
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mitsuhashi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ohta
authors.forename: Shingo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hoshi
authors.forename: Takanori
authors.initials: T
authors.lastname: Miki
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002478:Cells, Cultured; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism* / Q000502:physiology; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D007031:Hypothalamus / Q000166:cytology / Q000196:embryology*; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D020033:Protein Isoforms / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000097584:DNA Methyltransferase 3B; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D051783:Methyl-CpG-Binding Protein 2; D010636:Phenols; D020033:Protein Isoforms; D012313:RNA; D000097584:DNA Methyltransferase 3B; C000715535:Dnmt3a protein, mouse; C497393:Mecp2 protein, mouse; C000619381:Dnmt1 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds