Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6
Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6
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DOI：
10.1016/j.gene.2003.12.038
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发表时间：
2004-04-14
期刊：
影响因子：
3.5
通讯作者：
Simon, M
中科院分区：
文献类型：
--
作者：
Chavanas, S;Méchin, MC;Simon, M
肽基金氨氨酸脱氨酸酶（PADS）将蛋白质中的精氨酸残基转化为瓜氨酸。他们被怀疑参与多发性硬化症和类风湿关节炎病理生理学，并且在表皮稳态中发挥了作用，并且可能通过历史修饰来调节基因表达。在人类中，到目前为止已知由PADI1 -4基因编码的四种同工型。我们在这里分别在染色体LP35-36和4E1上报告了人（355 kb）和小鼠（240 kb）PAD基因簇的表征和比较分析。我们表征了一个尚未知道的人PADI6基因，并克隆了编码694-氨基酸蛋白的相应cDNA。 RT-PCR分析显示，组织特异性表达的模式相当有限，主要是在卵巢，睾丸和外周血白细胞中。核苷酸取代率表明PADI基因的纯化选择。人和小鼠序列的比较分析25 1主要聚集在启动子区域内的保守非编码段，每个基因PADI1 -3的大（> 10 kb）的第一内含子和8 kb Padi1 -2基因间区域。许多转录因子结合位点的存在表明这些段是推定的调节元素。这项研究是对人PADI6基因和编码蛋白的第一个描述，也是对PADI基因表达的协调调节的第一步。 （c）2004 Elsevier B.V.保留所有权利。
Peptidylarginine deiminases (PADs) convert arginine residues in proteins into citrullines. They are suspected to be involved in multiple sclerosis and rheumatoid arthritis pathophysiology, and they play a role in epidermis homeostasis and possibly in regulation of gene expression through historic modification. In humans, four isoforms encoded by the genes PADI1 -4 are known so far. We here report the characterization and comparative analysis of the human (355 kb) and mouse (240 kb) PAD gene clusters on chromosomes lp35-36 and 4E1, respectively. We characterized an as yet unknown human PADI6 gene, and cloned the corresponding cDNA encoding a 694-amino-acid protein. RT-PCR analysis showed a rather restricted pattern of tissue-specific expression, mainly in ovary, testis and peripheral blood leukocytes. Nucleotide substitution rates suggest that PADI genes are under purifying selection. Comparative analysis of the human and Mouse sequences identified 25 1 conserved non-coding segments predominantly clustered within the promoter regions, the large (>10 kb) first intron of each of the genes PADI1 -3, and an 8 kb PADI1 -2 intergenic region. The presence of numerous transcription factor binding sites suggests the segments are putative regulatory elements. This study is the first description of the human PADI6 gene and encoded protein, and the first step towards a better understanding of the coordinated regulation of PADI gene expression. (C) 2004 Elsevier B.V. All rights reserved.