title: Exposure to 3,3',5-triiodothyronine affects histone and RNA polymerase II modifications, but not DNA methylation status, in the regulatory region of the Xenopus laevis thyroid hormone receptor βΑ gene.
abstract: Thyroid hormones (THs) play a critical role in amphibian metamorphosis, during which the TH receptor (TR) gene, thrb, is upregulated in a tissue-specific manner. The Xenopus laevis thrb gene has 3 TH response elements (TREs) in the 5' flanking regulatory region and 1 TRE in the exon b region, around which CpG sites are highly distributed. To clarify whether exposure to 3,3',5-triiodothyronine (T3) affects histone and RNA polymerase II (RNAPII) modifications and the level of DNA methylation in the 5' regulatory region, we conducted reverse transcription-quantitative polymerase chain reaction, bisulfite sequencing and chromatin immunoprecipitation assay using X. laevis cultured cells and premetamorphic tadpoles treated with or without 2 nM T3. Exposure to T3 increased the amount of the thrb transcript, in parallel with enhanced histone H4 acetylation and RNAPII recruitment, and probably phosphorylation of RNAPII at serine 5, in the 5' regulatory and exon b regions. However, the 5' regulatory region remained hypermethylated even with exposure to T3, and there was no significant difference in the methylation status between DNAs from T3-untreated and -treated cultured cells or tadpole tissues. Our results demonstrate that exposure to T3 induced euchromatin-associated epigenetic marks by enhancing histone acetylation and RNAPII recruitment, but not by decreasing the level of DNA methylation, in the 5' regulatory region of the X. laevis thrb gene.
authors.affiliation: Department of Biological Science, Graduate School of Science, Shizuoka University, Shizuoka 422-8529, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Natural Sciences (Biology), School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Department of Biological Science, Graduate School of Science, Shizuoka University, Shizuoka 422-8529, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Biological Science, Graduate School of Science, Shizuoka University, Shizuoka 422-8529, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Otsuka
authors.affiliation: Department of Biological Science, Graduate School of Science, Shizuoka University, Shizuoka 422-8529, Japan; Green Biology Research Division, Research Institute of Green Science and Technology, Shizuoka University, Shizuoka 422-8529, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Ishihara
authors.affiliation: Department of Biological Science, Graduate School of Science, Shizuoka University, Shizuoka 422-8529, Japan; Green Biology Research Division, Research Institute of Green Science and Technology, Shizuoka University, Shizuoka 422-8529, Japan. Electronic address: yamauchi.kiyoshi@shizuoka.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamauchi
mesh_terms: D000818:Animals; D019175:DNA Methylation; D006657:Histones / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D014284:Triiodothyronine / Q000494:pharmacology*; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D006657:Histones; D037042:Thyroid Hormone Receptors beta; D029867:Xenopus Proteins; D014284:Triiodothyronine; D012319:RNA Polymerase II
keywords: DNA methylation; Histone modification; Thyroid hormone; Thyroid hormone receptor gene; Xenopus laevis