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.

Polycomb组（PCG）基因编码调节同源（HOX）基因和其他基因的转录阻遏物，并参与所谓的细胞记忆机制，这对于维持细胞身份至关重要。我们分离并表征了一种属于PCG基因的新型哺乳动物基因。从小鼠，大鼠和人脑中分离的cDNA的核苷酸序列分析表明，新型基因编码了蛋白质（863氨基酸），这些基因在氨基酸序列中表现出与Drosophila PCG PCG基因SCMEG SCMEG（seseg sexg on Midem commed on Midem comemem comemem comemem commenty of Midem Combens）的氨基酸序列相似性的显着相似性。此外，该蛋白包含MBT结构域的四个串联副本，最初在果蝇肿瘤抑制基因L（3）MBT（致命（3）恶性脑肿瘤）中报道了这些蛋白质。我们最初命名了这个新颖的基因SCML1（SCM oke-1），但此后将其改名为含有四个MBT域的SCM相关基因的SFMBT。鼠标SFMBT基因的插入和表征表明，编码序列揭示了包含20个exons，沿大约40 kb和人类映射的prombles ships the Gernal of the grouns和人类绘制了chremb，shite shembe shembe a prombb a prombb ship the sy prombb shimbb the shemb thembbt sfmbt gene。映射到3P21.1的映射到近的印迹分析表明，在成人睾丸中，SFMBT mRNA表达最丰富，但在所有小鼠组织和所检查的人类细胞系中的强度较少，但使用腺病毒的过表达实验表明，SFMBT Gene涉及HOXA的繁殖率，而HOXA的繁殖范围是HOXA的繁殖范围。在U251人神经胶质瘤细胞系中。这些功能数据很好地对应于属于PCG基因的SFMBT基因的结构数据，并类似于果蝇抑制基因L（3）MBT。为了研究SFMBT基因的突变表型，靶向诱变产生的SFMBT缺乏小鼠的实验现在正在储藏室中。