PDX-1 interaction and regulation of the Pancreatic Derived Factor (PANDER, FAM3B) promoter.
PDX-1 interaction and regulation of the Pancreatic Derived Factor (PANDER, FAM3B) promoter.
复制标题
PDX-1的相互作用和胰腺衍生因子（Pander，FAM3B）启动子的调节。
DOI：
10.1016/j.bbagrm.2008.07.007
复制
发表时间：
2008-10
影响因子：
4.7
通讯作者：
Wolf, Bryan A.
中科院分区：
文献类型：
--
作者：
Burkhardt, Brant R.;Cook, Joshua R.;Young, Robert A.;Wolf, Bryan A.
胰腺衍生因子（PANDER）是一种新的类胰蛋白酶蛋白，主要在胰腺内分泌表达。我们先前的研究表明PANDER启动子具有组织特异性和葡萄糖响应性。围绕PANDER转录起始位点的是几个推定的A盒和E盒元件，其可以结合MafA、BETA 2/NeuroD和胰腺十二指肠同源盒-1（PDX-1）的各种胰腺转录因子。为了表征参与PANDER基因表达的转录调控因子，我们进行了共转染报告基因分析，并证明了所有三种转录因子的上调，其中最大的个体增加来自PDX-1。通过染色质免疫沉淀（ChIP）证明PDX-1与PANDER启动子的A盒（TAAT）区域的潜在结合，并通过电泳迁移率变动测定（EMSA）进一步证实。PDX-1与A盒区域的结合被诱变（TAGT）寡核苷酸抑制。三个PDX-1 A盒结合基序的定点诱变显示，A盒位点2和3的组合对于最大基因表达至关重要，缺失导致启动子活性降低82%。此外，缺失A-box位点2和3完全降低了PANDER启动子的葡萄糖响应性。我们的研究结果表明，PANDER是一个潜在的PDX-1靶基因和启动子区域内的A盒位点是至关重要的基础和葡萄糖刺激的PANDER表达。
Pancreatic Derived Factor (PANDER) is a novel cytokine-like protein dominantly expressed within the endocrine pancreas. Our previous study demonstrated that the PANDER promoter was both tissue-specific and glucose-responsive. Surrounding the PANDER transcriptional start site are several putative A- and E-Box elements that may bind to the various pancreatic transcriptional factors of MafA, BETA2/NeuroD, and Pancreatic Duodenal Homeobox-1 (PDX-1). To characterize the transcriptional regulatory factors involved in PANDER gene expression, we performed co-transfection reporter gene analysis and demonstrated upregulation by all three transcription factors, with the greatest individual increase stemming from PDX-1. Potential binding of PDX-1 to A-box (TAAT) regions of the PANDER promoter was demonstrated by chromatin immunoprecipitation (ChIP) and further corroborated by electrophoretic mobility shift assay (EMSA). Binding of PDX-1 to the A box regions was inhibited by mutagenized (TAGT) oligonucleotides. Site-directed mutagenesis of the three PDX-1 A-box binding motifs revealed that A box sites 2 and 3 in combination were critical for maximal gene expression and deletion resulted in a 82% reduction in promoter activity. Furthermore, deletion of A-box sites 2 and 3 completely diminished the glucose-responsiveness of the PANDER promoter. Our findings demonstrate that PANDER is a potential PDX-1 target gene and the A-box sites within the promoter region are critical for basal and glucose-stimulated PANDER expression.
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影响因子：
4.8
作者：
Chakrabarti, SK;James, JC;Mirmira, RG
通讯作者：
Mirmira, RG
影响因子：
64.8
作者：
JONSSON, J;CARLSSON, L;EDLUND, H
通讯作者：
EDLUND, H
DOI：
10.1016/j.bbaexp.2005.07.003
发表时间：
2005-09-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Burkhardt, BR;Yang, MC;Wolf, BA
通讯作者：
Wolf, BA
影响因子：
8.2
作者：
Buteau, J;Roduit, R;Prentki, M
通讯作者：
Prentki, M
影响因子：
4.8
作者：
Iype, T;Francis, J;Mirmira, RG
通讯作者：
Mirmira, RG