The requirement of histone modification by PRDM12 and Kdm4a for the development of pre-placodal ectoderm and neural crest in Xenopus
The requirement of histone modification by PRDM12 and Kdm4a for the development of pre-placodal ectoderm and neural crest in Xenopus
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DOI：
10.1016/j.ydbio.2014.12.028
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发表时间：
2015-03-01
影响因子：
2.7
通讯作者：
Michiue, Tatsuo
中科院分区：
文献类型：
--
作者：
Matsukawa, Shinya;Miwata, Kyoko;Michiue, Tatsuo
在脊椎动物中，前基板外胚层和神经嵴的发展需要形态梯度和几个转录因子，而组蛋白修饰的参与仍然不清楚。在这里，我们报告组蛋白修饰因子在非洲爪蟾前基板外胚层和神经嵴的发育中起着至关重要的作用。在早期神经胚阶段，PRDM 12表达于外侧前基板外胚层，并通过组蛋白H3 K9的甲基化抑制神经嵴特异性基因的表达。ChIP-qPCR分析表明PRDM 12促进Foxd 3、Slug和Sox 8启动子上三甲基化组蛋白H3 K9（H3 K9 me 3）的占据。注射PRDM 12 MO抑制推定的三叉神经基板标志物的表达，并降低H3 K9 me 3在Foxd 3启动子上的占有率。组蛋白去甲基化酶Kdm 4a也以与PRDM 12 MO类似的方式抑制推定的三叉神经基板标记物的表达，并且可以补偿PRDM 12的作用。ChIP-qPCR分析显示，H3 K9 me 3在Foxd 3、Slug和Sox 8启动子上的占据的促进被Kdm 4a过表达抑制。两者合计，这些数据表明，组蛋白修饰是必不可少的前基板外胚层和神经嵴的发展。(C)2015爱思唯尔公司All rights reserved.
In vertebrates, pre-placodal ectoderm and neural crest development requires morphogen gradients and several transcriptional factors, while the involvement of histone modification remains unclear. Here, we report that histone-modifying factors play crucial roles in the development of pre-placodal ectoderm and neural crest in Xenopus. During the early neurula stage, PRDM12 was expressed in the lateral pre-placodal ectoderm and repressed the expression of neural crest specifier genes via methylation of histone H3K9. ChIP-qPCR analyses indicated that PRDM12 promoted the occupancy of the trimethylated histone H3K9 (H3K9me3) on the Foxd3, Slug, and Sox8 promoters. Injection of the PRDM12 MO inhibited the expression of presumptive trigeminal placode markers and decreased the occupancy of H3K9me3 on the Foxd3 promoter. Histone demethylase Kdm4a also inhibited the expression of presumptive trigeminal placode markers in a similar manner to PRDM12 MO and could compensate for the effects of PRDM12. ChIP-qPCR analyses revealed that promotion of the occupancy of H3K9me3 on the Foxd3, Slug, and Sox8 promoters was inhibited by Kdm4a overexpression. Taken together, these data indicate that histone modification was essential for pre-placodal ectoderm and neural crest development. (C) 2015 Elsevier Inc. All rights reserved.