Promoter-sharing by different genes in human genome--CPNE1 and RBM12 gene pair as an example.

Promoter-sharing by different genes in human genome--CPNE1 and RBM12 gene pair as an example.
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DOI:
10.1186/1471-2164-9-456
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发表时间:
2008-10-03
期刊:
影响因子:
4.4
通讯作者:
Lau YL
Lau YL
中科院分区:
生物学2区
文献类型:
--
作者:
Yang W;Ng P;Zhao M;Wong TK;Yiu SM;Lau YL

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基因表达调控在细胞功能中起着重要作用。不同基因的共同调控可能表明基因产物之间的功能连接甚至物理相互作用。因此,对可能影响基因表达调控的基因组结构的分析可以揭示基因的功能。在对选择性剪接事件的全基因组分析中,我们发现两个不同的基因,Copine I(CPNE1)和RNA结合基序蛋白12(RBM12),分享了人类最多的5‘外显子,因此也就是启动子区。进一步的分析发现,人类基因组中有许多基因对具有相同的启动子和5‘外显子,但具有完全不同的编码序列。对CPNE1和RBM12的基因组和表达序列的分析,无论是cDNA还是表达序列标签(EST),证实了这种现象在进化过程中的保守性。逆转录-聚合酶链式反应(RT-PCR)证实了同一启动子启动的两个基因在人和小鼠不同组织中的共表达。在CPNE1和RBM12共有的5‘非编码区中,多个物种之间的序列高度保守。在人、小鼠和斑马鱼中观察到CPNE1和RBM12之间存在启动子和5‘端非编码区的共享。在进化过程中这种基因组结构的保守表明这两个基因之间潜在的功能相互作用。在全基因组分析中发现,人类基因组中还有20多对基因具有相似的基因组结构,这可能代表了一种独特的基因组排列模式,可能影响相应基因的表达调控。
Regulation of gene expression plays important role in cellular functions. Co-regulation of different genes may indicate functional connection or even physical interaction between gene products. Thus analysis on genomic structures that may affect gene expression regulation could shed light on the functions of genes. In a whole genome analysis of alternative splicing events, we found that two distinct genes, copine I (CPNE1) and RNA binding motif protein 12 (RBM12), share the most 5' exons and therefore the promoter region in human. Further analysis identified many gene pairs in human genome that share the same promoters and 5' exons but have totally different coding sequences. Analysis of genomic and expressed sequences, either cDNAs or expressed sequence tags (ESTs) for CPNE1 and RBM12, confirmed the conservation of this phenomenon during evolutionary courses. The co-expression of the two genes initiated from the same promoter is confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) in different tissues in both human and mouse. High degrees of sequence conservation among multiple species in the 5'UTR region common to CPNE1 and RBM12 were also identified. Promoter and 5'UTR sharing between CPNE1 and RBM12 is observed in human, mouse and zebrafish. Conservation of this genomic structure in evolutionary courses indicates potential functional interaction between the two genes. More than 20 other gene pairs in human genome were found to have the similar genomic structure in a genome-wide analysis, and it may represent a unique pattern of genomic arrangement that may affect expression regulation of the corresponding genes.
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