title: Developmental and Thyroid Hormone Regulation of the DNA Methyltransferase 3a Gene in Xenopus Tadpoles.
abstract: Thyroid hormone is essential for normal development in vertebrates. In amphibians, T3 controls metamorphosis by inducing tissue-specific gene regulation programs. A hallmark of T3 action is the modification of chromatin structure, which underlies changes in gene transcription. We found that mRNA for the de novo DNA methyltransferase (DNMT) dnmt3a, but not dnmt1, increased in the brain of Xenopus tadpoles during metamorphosis in parallel with plasma [T3]. Addition of T3to the rearing water caused a time-dependent increase in dnmt3a mRNA in tadpole brain, tail, and hind limb. By analyzing data from a genome-wide analysis of T3 receptor (TR) binding in tadpole tail, we identified several putative T3 response elements (TREs) within the dnmt3a locus. Using in vitro DNA binding, transient transfection-reporter, and chromatin immunoprecipitation assays for TRs, we identified two functional TREs at -7.1 kb and +5.1 kb relative to the dnmt3a transcription start site. Sequence alignment showed that these TREs are conserved between two related frog species, X. laevis and X. tropicalis, but not with amniotes. Our previous findings showed that this gene is directly regulated by liganded TRs in mouse brain, and whereas the two mouse TREs are conserved among Eutherian mammals, they are not conserved in Xenopus species. Thus, although T3 regulation of dnmt3a may be an ancient pathway in vertebrates, the genomic sites responsible for hormone regulation may have diverged or arisen by convergent evolution. We hypothesize that direct T3regulation of dnmt3a may be an important mechanism for modulating global changes in DNA methylation.
authors: Neuroscience Graduate Program (Y.K.), The University of Michigan, Ann Arbor, Michigan 48109-1048; UMR-7221, Centre National de la Recherche Scientifique (L.M.S., P.B.), Muséum National d'Histoire Naturelle, 75005 Paris, France; and Department of Molecular, Cellular, and Developmental Biology (L.W., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109-1048.
authors: Yasuhiro
authors: Y
authors: Kyono
authors: Neuroscience Graduate Program (Y.K.), The University of Michigan, Ann Arbor, Michigan 48109-1048; UMR-7221, Centre National de la Recherche Scientifique (L.M.S., P.B.), Muséum National d'Histoire Naturelle, 75005 Paris, France; and Department of Molecular, Cellular, and Developmental Biology (L.W., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109-1048.
authors: Laurent M
authors: LM
authors: Sachs
authors: Neuroscience Graduate Program (Y.K.), The University of Michigan, Ann Arbor, Michigan 48109-1048; UMR-7221, Centre National de la Recherche Scientifique (L.M.S., P.B.), Muséum National d'Histoire Naturelle, 75005 Paris, France; and Department of Molecular, Cellular, and Developmental Biology (L.W., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109-1048.
authors: Patrice
authors: P
authors: Bilesimo
authors: Neuroscience Graduate Program (Y.K.), The University of Michigan, Ann Arbor, Michigan 48109-1048; UMR-7221, Centre National de la Recherche Scientifique (L.M.S., P.B.), Muséum National d'Histoire Naturelle, 75005 Paris, France; and Department of Molecular, Cellular, and Developmental Biology (L.W., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109-1048.
authors: Luan
authors: L
authors: Wen
authors: Neuroscience Graduate Program (Y.K.), The University of Michigan, Ann Arbor, Michigan 48109-1048; UMR-7221, Centre National de la Recherche Scientifique (L.M.S., P.B.), Muséum National d'Histoire Naturelle, 75005 Paris, France; and Department of Molecular, Cellular, and Developmental Biology (L.W., R.J.D.), The University of Michigan, Ann Arbor, Michigan 48109-1048.
authors: Robert J
authors: RJ
authors: Denver
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D007814:Larva; D008675:Metamorphosis, Biological / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014284:Triiodothyronine / Q000097:blood* / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: C000715535:Dnmt3a protein, mouse; D014284:Triiodothyronine; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A