Tomotsune D, Takihara Y, Berger J, Duhl D, Joo S, Kyba M, Shirai M, Ohta H, Matsuda Y, Honda B M, Simon J, Shimada K, Brock H W, Randazzo F
Department of Medical Genetics, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Differentiation. 1999 Dec;65(4):229-39. doi: 10.1046/j.1432-0436.1999.6540229.x.
The Polycomb group of (PcG) genes were originally described in Drosophila, but many PcG genes have mammalian homologs. Genetic studies in flies and mice show that mutations in PcG genes cause posterior transformations caused by failure to maintain repression of homeotic loci, suggesting that PcG proteins have conserved functions. The Drosophila gene Sex comb on midleg (Scm) encodes an unusual PcG protein that shares motifs with the PcG protein polyhomeotic, and with a Drosophila tumor suppressor, lethal(3)malignant brain tumor (l(3)mbt). Expressed sequence tag (EST) databases were searched to recover putative mammalian Scm homologs, which were used to screen murine cDNA libraries. The recovered cDNA encodes two mbt repeats and the SPM domain that characterize Scm, but lacks the cysteine clusters and the serine/threonine-rich region found at the amino terminus of Scm. Accordingly, we have named the gene Sex comb on midleg homolog 1 (Scmh1). Like their Drosophila counterparts, Scmh1 and the mammalian polyhomeotic homolog RAE28/mph1 interact in vitro via their SPM domains. We analyzed the expression of Scmh1 and rae28/mph1 using northern analysis of embryos and adult tissues, and in situ hybridization to embryos. The expression of Scmh1 and rae28/mph1 is well correlated in most tissues of embryos. However, in adults, Scmh1 expression was detected in most tissues, whereas mph1/rae28 expression was restricted to the gonads. Scmh1 is strongly induced by retinoic acid in F9 and P19 embryonal carcinoma cells. Scmh1 maps to 4D1-D2.1 in mice. These data suggest that Scmh1 will have an important role in regulation of homeotic genes in embryogenesis and that the interaction with RAE28/mph1 is important in vivo.
多梳蛋白家族（PcG）基因最初是在果蝇中被发现的，但许多PcG基因在哺乳动物中存在同源物。对果蝇和小鼠的遗传学研究表明，PcG基因的突变会导致同源异型基因座抑制失败而引起的后部转化，这表明PcG蛋白具有保守功能。果蝇基因中腿上的性梳（Scm）编码一种不寻常的PcG蛋白，它与PcG蛋白多同源异型蛋白以及果蝇肿瘤抑制因子致死（3）恶性脑肿瘤（l（3）mbt）共享基序。通过搜索表达序列标签（EST）数据库来寻找推定的哺乳动物Scm同源物，并用其筛选小鼠cDNA文库。回收的cDNA编码两个mbt重复序列和表征Scm的SPM结构域，但缺少在Scm氨基末端发现的半胱氨酸簇和富含丝氨酸/苏氨酸的区域。因此，我们将该基因命名为中腿上的性梳同源物1（Scmh1）。与它们在果蝇中的对应物一样，Scmh1和哺乳动物多同源异型蛋白同源物RAE28/mph1在体外通过它们的SPM结构域相互作用。我们通过对胚胎和成年组织进行Northern分析以及对胚胎进行原位杂交来分析Scmh1和rae28/mph1的表达。Scmh1和rae28/mph1的表达在胚胎的大多数组织中具有良好的相关性。然而，在成体中，Scmh1在大多数组织中都能检测到表达，而mph1/rae28的表达则局限于性腺。视黄酸在F9和P19胚胎癌细胞中强烈诱导Scmh1表达。Scmh1在小鼠中定位于4D1-D2.1。这些数据表明，Scmh1在胚胎发育过程中对同源异型基因的调控中将发挥重要作用，并且与RAE28/mph1的相互作用在体内很重要。
