Multiple regulatory regions and tissue-specific transcription initiation mediate the expression of NEMO/IKKγ gene
Multiple regulatory regions and tissue-specific transcription initiation mediate the expression of NEMO/IKKγ gene
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DOI：
10.1016/j.gene.2006.07.022
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发表时间：
2006-11-15
期刊：
影响因子：
3.5
通讯作者：
Ursini, Matilde Valeria
中科院分区：
文献类型：
--
作者：
Fusco, Francesca;Mercadante, Vincenzo;Ursini, Matilde Valeria
ATEMO/IKKy基因编码的蛋白在NF-κ B通路的激活中具有重要的调节作用，是人类两种等位基因疾病EDA-1D和IP的致病基因。我们在这里提供的NEMO/IKK γ表达的分子调控机制的见解。我们映射了4个独特的NEMO/IKK γ转录起始位点，每个对应于一个替代的第一外显子，由两个保守的启动子控制。远端启动子A位于编码区上游10 kb处，近端启动子B具有强的双向活性，也驱动G6 PD基因的反向转录。启动子B是管家，它嵌入在CpG岛中，是正确表达所需的，并且它通过甲基化下调。启动子A在肝来源的细胞中是有活性的，并且它指导肝中主要NEMO/IKKy 5' UTR替代转录物的转录，其起始于组织特异性位点。定性和定量表达分析显示，每个NEMO/IKK γ 5' UTR替代转录物具有不同的表达谱，表明NEMO/IKK γ表达的控制是通过组织特异性转录起始位点和多个调控区域介导的。(c)2006 Elsevier B. V.保留所有权利。
ATEMO/IKKy gene, which is responsible of two allelic diseases in human, EDA-1D and IP, encodes for a protein with a central regulatory role in the activation of the NF-kB pathway. We here provide insights into the molecular rriechanism governing NEMO/IKK gamma expression. We mapped 4 distinctive NEMO/IKK gamma transcription start sites each corresponding to an alternative first exon, controlled by two conserved promoters. A distal promoter, named promoter A, located 10 kb upstream of the coding region and a proximal promoter, promoter B, with strong bi-directional activity driving also the transcription of G6PD gene in the opposite direction. The promoter B is housekeeping, it is embedded in a CpG island, required for proper expression and it is down-regulated by methylation. The promoter A is active in cells of hepatic origin and it directs transcription of the main NEMO/IKKy 5' UTR alternative transcript in liver, which starts at a tissue-specific site. Qualitative and quantitative expression analysis revealed that each NEMO/IKK gamma 5' UTR alternative transcript has different expression profiles indicating that the control of NEMO/IKK gamma expression is mediated through tissue-specific transcription initiation sites and multiple regulatory regions. (c) 2006 Elsevier B.V. All rights reserved.