title: New insights into the role of Jmjd3 and Utx in axial skeletal formation in mice.
abstract: Jmjd3 and Utx are demethylases specific for lysine 27 of histone H3. Previous reports indicate that Jmjd3 is essential for differentiation of various cell types, such as macrophages and epidermal cells in mice, whereas Utx is involved in cancer and developmental diseases in humans and mice, as well asHoxregulation in zebrafish and nematodes. Here, we report that Jmjd3, but not Utx, is involved in axial skeletal formation in mice. A Jmjd3 mutant embryo (Jmjd3Δ18/Δ18), but not a catalytically inactive Utx truncation mutant (Utx-/y), showed anterior homeotic transformation. Quantitative RT-PCR and microarray analyses showed reducedHoxexpression in bothJmjd3Δ18/Δ18embryos and tailbuds, whereas levels ofHoxactivators, such as Wnt signaling factors and retinoic acid synthases, did not decrease, which suggests that Jmjd3 plays a regulatory role inHoxexpression during axial patterning. Chromatin immunoprecipitation analyses of embryo tailbud tissue showed trimethylated lysine 27 on histone H3 to be at higher levels at theHoxloci inJmjd3Δ18/Δ18mutants compared with wild-type tailbuds. In contrast, trimethylated lysine 4 on histone H3 levels were found to be equivalent in wild-type andJmjd3Δ18/Δ18tailbuds. Demethylase-inactive Jmjd3 mutant embryos showed the same phenotype asJmjd3Δ18/Δ18mice. These results suggest that the demethylase activity of Jmjd3, but not that of Utx, affects mouse axial patterning in concert with alterations inHoxgene expression.-Naruse, C., Shibata, S., Tamura, M., Kawaguchi, T., Abe, K., Sugihara, K., Kato, T., Nishiuchi, T., Wakana, S., Ikawa, M., Asano, M. New insights into the role of Jmjd3 and Utx in axial skeletal formation in mice.
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Naruse
authors.affiliation: Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Shinwa
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Abe
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan.|Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugihara
authors.affiliation: Division of Functional Genomics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kato
authors.affiliation: Division of Functional Genomics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Nishiuchi
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
authors.affiliation: Animal Resource Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan; asano@anim.med.kyoto-u.ac.jp.|Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D001842:Bone and Bones / Q000196:embryology* / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; D056466:Histone Demethylases; D056484:Jumonji Domain-Containing Histone Demethylases; C111778:Utx protein, mouse; C523761:Kdm6b protein, mouse
keywords: H3K27 methylation; Hox; histone demethylation; homeotic transformation; kyphosis