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生长激素转录因子ZN-16的基因组编码区由单个外显子组成,并且在哺乳动物中具有进化保守性。

Growth hormone transcription factor ZN-16 genomic coding regions are composed of a single exon and are evolutionarily conserved in mammals.

作者信息

Flynn Maxfield P, Hurley David L

机构信息

Department of Biochemistry, Tulane University School of Medicine, New Orleans, LA, USA.

出版信息

Gene. 2006 Mar 1;368:78-83. doi: 10.1016/j.gene.2005.10.010. Epub 2005 Nov 21.

Abstract

The structure of the gene encoding ZN-16, a transcription factor that binds to the mammalian growth hormone promoter in tandem with Pit-1, was determined in order to elucidate the exon-intron organization of the 16 zinc finger domains of the protein. Southern hybridization of mouse genomic DNA showed fragments with sizes identical to those predicted from mouse ZN-16 cDNA for two different probes covering the 2200 aa coding frame. Mouse genome database sequences also showed no introns in the zn-16 coding regions on chromosome 4. Analysis of human zn-16 by Southern hybridization and genomic database sequence analysis also indicated a single exon for the human protein coding sequences. BLASTP query of available genomic databases with critical zinc finger residues from mouse ZN-16 identified highly similar canine, bovine, and chimpanzee genomic sequences that encode proteins. Phylogenetic analysis of these mammalian proteins resulted in relationships as would be expected in species spanning rodents to humans. All six independent zn-16 sequences show a single exon coding region with no introns, a similarity ruling out the possibility that these genomic sequences are pseudogenes. Thus, mammalian zn-16 has a compact single exon structure encoding a very large protein (2200-3000 aa), the conservation of which may have functional implications such as the importance of posttranscriptional modifications.

摘要

为了阐明与Pit-1协同结合哺乳动物生长激素启动子的转录因子ZN-16的16个锌指结构域的外显子-内含子组织,对编码ZN-16的基因结构进行了测定。小鼠基因组DNA的Southern杂交显示,对于覆盖2200个氨基酸编码框的两种不同探针,片段大小与从小鼠ZN-16 cDNA预测的大小相同。小鼠基因组数据库序列也显示4号染色体上的zn-16编码区域没有内含子。通过Southern杂交和基因组数据库序列分析对人zn-16进行分析,也表明人蛋白质编码序列为单个外显子。用小鼠ZN-16的关键锌指残基对可用基因组数据库进行BLASTP查询,鉴定出编码蛋白质的高度相似的犬、牛和黑猩猩基因组序列。对这些哺乳动物蛋白质进行系统发育分析,得到的关系与从啮齿动物到人类的物种预期一致。所有六个独立的zn-16序列都显示出一个没有内含子的单个外显子编码区域,这种相似性排除了这些基因组序列是假基因的可能性。因此,哺乳动物的zn-16具有紧凑的单个外显子结构,编码一个非常大的蛋白质(2200 - 3000个氨基酸),其保守性可能具有功能意义,例如转录后修饰的重要性。

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