Participation of Polycomb group gene extra sex combs in hedgehog signaling pathway.
Polycomb group (PcG) genes are required for stable inheritance of epigenetic states across cell divisions, a phenomenon termed cellular memory. PcG proteins form multimeric nuclear complex which modifies the chromatin structure of target site. Drosophila PcG gene extra sex combs (esc) and its vertebrate orthologs constitute a member of ESC-E(Z) complex, which possesses histone methyltransferase activity. Here we report isolation and characterization of medaka esc homolog, termed oleed. Hypomorphic knock-down of oleed using morpholino antisense oligonucleotides resulted in the fusion of eyes, termed cyclopia. Prechordal plate formation was not substantially impaired, but expression of hedgehog target genes was dependent on oleed, suggesting some link with hedgehog signaling. In support of this implication, histone methylation, which requires the activity of esc gene product, is increased in hedgehog stimulated mouse NIH-3T3 cells. Our data argue for the novel role of esc in hedgehog signaling and provide fundamental insight into the epigenetic mechanisms in general.
Shindo
Norihisa
N
Department of Biology, School of Education and Major in Integrated Bioscience and Biomedical Engineering, Graduate School of Science and Engineering, Waseda University, 1-6-1 Nishi-Waseda, Shinjuku, Tokyo 169-8050, Japan.
Sakai
Atsushi
A
Yamada
Kouji
K
Higashinakagawa
Toru
T
D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D008969:Molecular Sequence Data; D009990:Oryzias / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; C066770:Pc protein, Drosophila; D063146:Polycomb-Group Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; C543389:esc protein, Drosophila; D063150:Polycomb Repressive Complex 1