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SOX2直系同源基因的比较基因组学

Comparative genomics on SOX2 orthologs.

作者信息

Katoh Yuriko, Katoh Masaru

机构信息

M&M Medical BioInformatics, Hongo 113-0033, Japan.

出版信息

Oncol Rep. 2005 Sep;14(3):797-800.

PMID:16077994
Abstract

SOX2 and POU5F1 (OCT3 or OCT4) transcription factors are implicated in FGF4 expression in embryonic stem (ES) cells. SOX2, POU5F1, and FGF4 are key molecules for the integrome network in oncology and stem cell biology. SOX2 gene at human chromosome 3q26.33, SOX1 gene at 13q34, and SOX3 gene at Xq27.1 constitute a subfamily among the SOX gene family. Here, rat Sox2 and Xenopus sox2 genes were identified and characterized by using bioinformatics for comparative genomics and comparative proteomics analyses. Rat Sox2 gene, encoding a 319-aa protein, was located around the nucleotide position 73213-75621 of rat genome sequence AC123231.4. Xenopus tropicalis sox2 complete coding sequence, encoding a 311-aa protein, was derived from CR760314.1 cDNA. Rat Sox2 showed 98.4%, 97.8%, 92.2%, 88.1% and 86.8% total amino-acid identity with mouse Sox2, human SOX2, chicken sox2, Xenopus sox2 and zebrafish sox2, respectively. SOX123C domain was identified as the novel domain corresponding to the C-terminal region conserved among SOX1, SOX2 and SOX3 orthologs. Vertebrate SOX1, SOX2 and SOX3 orthologs were found consisting of HMG box and SOX123C domain. SOX9, TCF/LEF, POU2F1 and COMP1 binding sites were conserved among human SOX2 promoter, rat Sox2 promoter, and mouse Sox2 promoter. SOX2 mRNA was expressed in ES cells, fetal brain, anaplastic oligodendroglioma, rhabdomyosarcoma, and small cell lung carcinoma. Due to the pivotal role of SOX2 in the early embryogenesis, SOX2 promoter and SOX2 protein were well conserved during vertebrate evolution. This is the first report on comparative integromics analyses on the SOX2 orthologs.

摘要

SOX2和POU5F1(OCT3或OCT4)转录因子与胚胎干细胞(ES细胞)中的FGF4表达有关。SOX2、POU5F1和FGF4是肿瘤学和干细胞生物学中整合基因组网络的关键分子。人类染色体3q26.33上的SOX2基因、13q34上的SOX1基因和Xq27.1上的SOX3基因构成了SOX基因家族中的一个亚家族。在此,通过生物信息学进行比较基因组学和比较蛋白质组学分析,鉴定并表征了大鼠Sox2基因和非洲爪蟾sox2基因。大鼠Sox2基因编码一种319个氨基酸的蛋白质,位于大鼠基因组序列AC123231.4的核苷酸位置73213 - 75621附近。热带爪蟾sox2完整编码序列编码一种311个氨基酸的蛋白质,来源于CR760314.1 cDNA。大鼠Sox2与小鼠Sox2、人类SOX2、鸡sox2、非洲爪蟾sox2和斑马鱼sox2的总氨基酸同一性分别为98.4%、97.8%、92.2%、88.1%和86.8%。SOX123C结构域被鉴定为与SOX1、SOX2和SOX3直系同源物中保守的C末端区域相对应的新结构域。发现脊椎动物的SOX1、SOX2和SOX3直系同源物由HMG框和SOX123C结构域组成。人类SOX2启动子、大鼠Sox2启动子和小鼠Sox2启动子中SOX9、TCF/LEF、POU2F1和COMP1结合位点保守。SOX-2 mRNA在ES细胞、胎儿脑、间变性少突胶质细胞瘤、横纹肌肉瘤和小细胞肺癌中表达。由于SOX2在早期胚胎发育中的关键作用,SOX2启动子和SOX2蛋白在脊椎动物进化过程中高度保守。这是关于SOX2直系同源物比较整合基因组学分析的首次报道。

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