TY - JOUR
T1 - The ESC-E(Z) complex participates in the hedgehog signaling pathway
AU - Shindo, Norihisa
AU - Sakai, Atsushi
AU - Arai, Daisuke
AU - Matsuoka, Osamu
AU - Yamasaki, Yukihiko
AU - Higashinakagawa, Toru
N1 - Funding Information:
We thank A. Kanamori for a medaka ovarian cDNA library, D. Kobayashi and K. Araki for an shh probe, J. Wittbrodt for spalt and Pax2 probes, K. Inohaya for technical advice, Y. Ishikawa for the medaka HO4C strain, T. Jenuwein and S. Opravil for anti-methylated histone H3 antibodies, and M. Sasaki for technical assistance. Financial support was provided by Special Coordination Funds from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a Grant-in-Aid to the Research Center for Genomic Medicine, Saitama Medical School, from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2005/2/25
Y1 - 2005/2/25
N2 - 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.
AB - 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.
KW - Cellular memory
KW - Cyclopia
KW - Enhancer of zeste
KW - Epigenetics
KW - Extra sex combs
KW - Histone methylation
KW - Knock-down
KW - Medaka
KW - Polycomb group
KW - hedgehog signaling
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U2 - 10.1016/j.bbrc.2004.12.125
DO - 10.1016/j.bbrc.2004.12.125
M3 - Article
C2 - 15652519
AN - SCOPUS:12344272717
SN - 0006-291X
VL - 327
SP - 1179
EP - 1187
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -