Kanda Miyuki, Wada Hiroshi, Fujiwara Shigeki
Department of Applied Science, Kochi University, Akebono-cho, Kochi-shi, Japan.
Dev Biol. 2009 Nov 15;335(2):454-63. doi: 10.1016/j.ydbio.2009.09.027. Epub 2009 Sep 25.
Hox genes play important roles in the specification of spatial identity during development of vertebrate embryos. Retinoic acid regulates the transcription of Hox genes in vertebrates. We identified an epidermal enhancer in the 5' flanking region of an ortholog of Hox1 (Ci-Hox1) in the ascidian Ciona intestinalis. This enhancer element drives the transcription of a lacZ reporter gene in the epidermis in the posterior trunk and the anterior tail region of tailbud-stage embryos. Inhibition of retinoic acid synthesis resulted in inactivation of the expression of the reporter gene. The enhancer contains a putative retinoic acid response element. When this element was mutagenized, the expression of the reporter gene disappeared from the epidermis. This sequence was also required for the response to exogenously administered retinoic acid. A heterodimeric nuclear receptor, consisting of the retinoic acid receptor and retinoid X receptor, bound to this sequence. These results indicate that retinoic acid directly activates the epidermal enhancer of Ci-Hox1. This is the first demonstration that retinoic acid is necessary for endogenous gene expression in ascidian embryos.
Hox基因在脊椎动物胚胎发育过程中对空间身份的特化起着重要作用。视黄酸调节脊椎动物中Hox基因的转录。我们在海鞘Ciona intestinalis的Hox1直系同源基因（Ci-Hox1）的5'侧翼区域鉴定出一个表皮增强子。该增强子元件驱动尾芽期胚胎后躯干部和前尾区域表皮中lacZ报告基因的转录。视黄酸合成的抑制导致报告基因表达失活。该增强子包含一个假定的视黄酸反应元件。当该元件发生诱变时，报告基因的表达从表皮消失。该序列对外源施用视黄酸的反应也是必需的。由视黄酸受体和类视黄醇X受体组成的异二聚体核受体与该序列结合。这些结果表明视黄酸直接激活Ci-Hox1的表皮增强子。这是视黄酸对海鞘胚胎内源性基因表达必不可少的首次证明。
