title: The ESC-E(Z) complex participates in the hedgehog signaling pathway.
abstract: Polycomb group (PcG) genes are required for stable inheritance of epigenetic states throughout development, a phenomenon termed cellular memory. In Drosophila and mice, the product of the E(z) gene, one of the PcG genes, constitutes the ESC-E(Z) complex and specifically methylates histone H3. It has been argued that this methylation sets the stage for appropriate repression of certain genes. Here, we report the isolation of a well-conserved homolog of E(z), olezh2, in medaka. Hypomorphic knock-down of olezh2 resulted in a cyclopia phenotype and markedly perturbed hedgehog signaling, consistent with our previous report on oleed, a medaka esc. We also found cyclopia in embryos treated with trichostatin A, an inhibitor of histone deacetylase, which is a transient component of the ESC-E(Z) complex. The level of tri-methylation at lysine 27 of histone H3 was substantially decreased in both olezh2 and oleed knock-down embryos, and in embryos with hedgehog signaling perturbed by forskolin. We conclude that the ESC-E(Z) complex per se participates in hedgehog signaling.
authors.affiliation: Department of Biology, Faculty of Education and Integrated Arts and Sciences, Major in Integrated Bioscience and Biomedical Engineering, Graduate School of Science and Engineering, Waseda University, 1-6-1 Nishi-Waseda, Shinjuku-ku, Tokyo 169-8050, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Shindo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Arai
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuoka
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Toru
authors.initials: T
authors.lastname: Higashinakagawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D029941:Fish Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009990:Oryzias / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010802:Phylogeny; D011485:Protein Binding; D016415:Sequence Alignment; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D029941:Fish Proteins; D053823:Hedgehog Proteins; D006657:Histones; D006877:Hydroxamic Acids; D046912:Multiprotein Complexes; D015534:Trans-Activators; C012589:trichostatin A; D008239:Lysine