Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors
Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors
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DOI：
10.1111/j.0022-202x.2005.23690.x
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发表时间：
2005-05-01
影响因子：
6.5
通讯作者：
Takahara, H
中科院分区：
文献类型：
--
作者：
Dong, SJ;Kojima, T;Takahara, H
肽基精氨酸脱亚胺酶(PAD)以钙离子依赖的方式将蛋白质结合的精氨酸残基转化为瓜氨酸残基。在啮齿动物和人类中存在的五种亚型(PAD1、2、3、4和6)中，PAD2在物种、组织和器官中表达最广泛。为了研究人PAD2基因PADI2的表达调控机制，我们利用转基因的人角质形成细胞对其启动子区域进行了鉴定。从转录起始点上游的2kb区域衍生的一系列报告基因结构定义了一个从-132到-41的最小启动子序列。该PADI2区富含GC，缺乏典型的TATA和CAAT盒。对该区域顺式作用元件的研究、进一步的缺失分析和使用特异性抗体的电泳迁移率改变分析发现了四个Sp1结合位点，并确定Sp1和Sp3是影响启动子活性的重要结合因子。这些结果表明，Sp1/Sp3的协同作用可能为控制PADI2的转录提供了一种机制。
Peptidylarginine deiminases (PAD) convert protein-bound arginine residues into citrulline residues in a Ca2+ ion-dependent manner. Among the five isoforms (PAD1, 2, 3, 4, and 6) existing in rodents and humans, PAD2 is the most widely expressed in both species, tissues, and organs. In order to study the mechanisms regulating the expression of the human PAD2 gene, PADI2, we characterized its promoter region using transfected human keratinocytes. A series of reporter gene constructions derived from the 2 kb region upstream of the transcription initiation site defined a minimal promoter sequence from nucleotides -132 to -41. This PADI2 region is GC-rich and lacks canonical TATA and CAAT boxes. Investigation of cis-acting elements in the region, further deletion analyses and electrophoretic mobility shift assays using specific antibodies revealed four Sp1-binding sites and identified Sp1 and Sp3 as binding factors important for the promoter activity. These results suggest that Sp1/Sp3 cooperation may provide a mechanism to control the transcription of PADI2.