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Structural and functional characterization of a novel Polycomb group gene SCML1.

新型 Polycomb 组基因 SCML1 的结构和功能表征。

基本信息

批准号：
11680736
负责人：
USUI Hiroshi
金额：
$ 2.43万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680736/
关键词：
Sfmbt gene Polycomb group genes brain tumor HOX gene glioma knockout mice ホリコーム遺伝子群 Polycomb-group gene Sfmbt mbt repeats

项目摘要

Polycomb group (PcG) genes encode transcriptional repressors which regulate homeotic (HOX) genes and others, and are involved in so-called cellular memory mechanisms which is essential in the maintenance of cell identity. We isolated and characterized a novel mammalian gene belonging to the PcG genes.The nucleotide sequence analysis of the cDNAs isolated from the mouse, rat, and human brain revealed that the novel gene encoded the protein (863 amino acids) that showed significant similarity in amino acid sequence to the product of Drosophila PcG gene Scm (Sex comb on midleg). In addition, this protein contained four tandem copies of the mbt domains, which were originally reported in the Drosophila tumor suppressor gene l(3)mbt (lethal(3) malignant brain tumor). We initially named this novel gene SCML1 (Scm like-1), but thereafter renamed it Sfmbt for Scm-related gene containing four mbt domains.Cloning and characterization of the mouse Sfmbt gene revealed that the coding sequence comprised 20 exons, dispersed along approximately 40 kb, and was mapped to the proximal part of Chromosome 14. The human Sfmbt gene was mapped to the chromosome 3p21.1.Northern blot analysis showed that the Sfmbt mRNAs were expressed most abundantly in the adult testis, but less intensively in all the mouse tissues and human cell lines examined.Transient over-expression experiments using adenovirus vector indicated that the Sfmbt gene was involved in the regulation of HOXA1 gene expression, and the modification of the cell proliferation rate in U251 human glioma cell line. These functional data well correspond to the structural data of the Sfmbt gene that belongs to the PcG genes and resembles the Drosophila tumor suppressor gene l(3)mbt. To investigate the mutated phenotype of the Sfmbt gene, the experiment on Sfmbt-deficient mice, generated by targeted mutagenesis, is now in progres.

多梳组（Polycomb group，PcG）基因编码转录抑制因子，调控同源异型（homeotic，HOX）基因等，参与细胞记忆机制，对维持细胞身份至关重要。我们分离并鉴定了一个属于PcG基因的哺乳动物新基因，对小鼠、大鼠和人脑cDNA的核苷酸序列分析表明，该基因编码的蛋白质（863个氨基酸）与果蝇PcG基因Scm（Sex comb on midleg）的产物在氨基酸序列上具有显著的相似性。此外，该蛋白质含有四个串联拷贝的mbt结构域，其最初在果蝇肿瘤抑制基因l（3）mbt（致死性（3）恶性脑肿瘤）中报道。我们最初将该基因命名为SCML 1（Scm like-1），后来又将其命名为Sfmbt（Scm related gene，含4个mbt结构域），克隆并鉴定了小鼠Sfmbt基因，其编码序列由20个外显子组成，分布在沿着约40 kb的区域，定位于14号染色体的近端。Northern杂交结果表明，人Sfmbt基因在成年小鼠睾丸中表达最丰富，而在小鼠组织和人细胞系中表达较弱，腺病毒瞬时过表达实验表明，人Sfmbt基因参与HOXA 1基因的表达调控，并对U251胶质瘤细胞系的细胞增殖率进行了调节。这些功能数据很好地对应于Sfmbt基因的结构数据，该基因属于PcG基因，并类似于果蝇肿瘤抑制基因l（3）mbt。为了研究Sfmbt基因的突变表型，通过靶向诱变产生的Sfmbt缺陷小鼠的实验正在进行中。