Participation of Polycomb group gene extra sex combs in hedgehog signaling pathway.

Participation of Polycomb group gene extra sex combs in hedgehog signaling pathway.
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Polycomb组基因额外性梳参与hedgehog信号通路。

DOI:
10.1016/j.bbrc.2004.08.125
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发表时间:
2004
影响因子:
3.1
通讯作者:
T. Higashinakagawa
T. Higashinakagawa
中科院分区:
生物学4区
文献类型:
--
作者:
Norihisa Shindo;A. Sakai;K. Yamada;T. Higashinakagawa

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聚梳组(PcG)基因是细胞分裂过程中表观遗传状态稳定遗传所必需的,这种现象被称为细胞记忆。PCG蛋白形成多聚体核复合体,改变靶部位的染色质结构。果蝇PcG基因ESC及其脊椎动物同源基因构成ESC-E(Z)复合体的一员,具有组蛋白甲基转移酶活性。在这里,我们报告了青竹ESC同系物的分离和鉴定,称为OLEED。使用吗啉反义寡核苷酸亚形击倒青光眼,导致眼睛融合,称为睫状眼。前索前板的形成并未受到实质性的损害,但Hedgehog靶基因的表达依赖于OLEED,这表明Hedgehog信号与Hedgehog信号有关。在刺猬刺激的小鼠NIH-3T3细胞中,需要ESC基因产物活性的组蛋白甲基化增加,这支持了这一点。我们的数据证明了ESC在刺猬信号中的新作用,并为总体上的表观遗传机制提供了基本的见解。
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.
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