Structure and function of the transcription factor AREC3

1. 从小鼠骨骼肌cDNA文库中克隆了3个编码AREC3/Six4蛋白的cDNA。序列分析表明，AREC3是6个新基因家族的成员，具有同源结构域和6结构域作为保守结构域。这两个结构域都是特定DNA结合所必需的，潜在的反激活结构域位于C端部分。在成肌细胞系C2C12的分化过程中，细胞质中诱导了AREC3蛋白的产生。在大鼠出生后视网膜形成过程中，该基因产物的表达模式变化很大。这些观察结果表明该基因参与了发育和分化过程。从小鼠视网膜cDNA文库中分离到Six2、Six3、Six5等6个家族基因。这些基因通过原位杂交显示在视网膜中表达。同源域（Homeodomain）和六域（sixdomain）作为特异性的DNA结合域，在Six2、Six4和Six5.3中，DNA的结合特异性是保守的。采用免疫组化方法分析了新生大鼠视网膜和成年大鼠脑内are3蛋白的分布。在PND（出生后）1中，AREC3蛋白位于神经节细胞的细胞核中，在PND4中，除PND1外，该蛋白在内核层表达，在PND7中，在内核层外细胞中表达。在神经节细胞中，PND13的表达从细胞核转移到细胞质，蛋白在外节段和内节段表达。PND20后，细胞核内未见分布。在大鼠脑中，在海马和梨状皮质的细胞核中观察到AREC3蛋白，在细胞质中观察到mRNA。在小鼠胚胎E9.5期的神经元细胞核中检测到AREC3蛋白。AREC3在神经元和视网膜的分化和发育中起重要作用，在E10.5 ~ E11.5时达到峰值，在e14.5时逐渐下降到不可检测的水平。少

1. Three species of cDNA encoding AREC3/Six4 protein has been cloned from mouse skeletal muscle cDNA library. Sequence analysis revealed that the AREC3 is a member of new gene family of Six which has homeodomain and sixdomain as conserved domains. Both of the domains are necessary for specific DNA binding, and potential transactivation domain resides in the C terminal portion. During the differentiation of myoblast cell line C2C12, the productio of AREC3 protein is induced in the cytoplasm. During postnatal retina formation in rat, the expression pattern of the gene product varies dramatically. These observations suggest that the gene is involved in development and differentiation process.2. Other members of Six family genes, Six2, Six3 and Six5 cDNAs were isolated from mouse retina cDNA library. These genes were shown to be expressed in retina by in situ hybridization. Homeodomain and sixdomain function as a specific DNA binding domain, and the DNA binding specificity was conserved am … More ong Six2, Six4 and Six5.3. The distribution of AREC3 protein was analyzed by immunohistochemistry in newborn the rat retina and in the adult rat brain. In PND (postnatal day)1, the AREC3 resided in the nucleus of ganglion cells, in PND4, in addition to PND1, the protein was expressed in the inner nuclear layr and in PND7, the expression was observed in outer cells of the inner nuclear layr. In PND13, the expression was moved from the nucleus to the cytoplasm in ganglion cells, and the protein was expressed in outer segment and inner segment. After PND20, no distribution in the nucleus was observed. In rat brain, AREC3 protein was observed in the cell nucleus in hippocampus and in the piriform cortex and the mRNA was observed in the cytoplasm.4. In the mouse embryo, the AREC3 protein was detected in the nucleus of neuronal cells from stage E9.5. The production peaks at E10.5 to E11.5 and then gradually declined to undetectable level at E14.5These results indicates that the AREC3 plays an important role in differentiation and development of neuron and retina. Less