Involvement of the homeodomain-containing transcription factor PDX-1 in islet amyloid polypeptide gene transcription
Involvement of the homeodomain-containing transcription factor PDX-1 in islet amyloid polypeptide gene transcription
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DOI：
10.1006/bbrc.1996.1875
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发表时间：
1996-12-24
影响因子：
3.1
通讯作者：
Yamasaki, Y
中科院分区：
文献类型：
--
作者：
Watada, H;Kajimoto, Y;Yamasaki, Y
胰岛素基因启动子的富含AT的eis基序A元件有助于将基因的表达引导至胰腺β细胞，由含同源异型蛋白的转录因子PDX-1/IPF 1/STF-1/IDX-1结合。胰岛淀粉样多肽（IAPP;胰淀素）基因，也表达在有限的组织，如胰腺β-和δ-细胞，含有类似的AT丰富的序列在其调控序列。为了了解IAPP基因调控的分子基础，我们评估了该基序在人类IAPP基因调控中可能的生理意义。与CT盒共有序列匹配的所有三种典型的A元件样序列（AT-1，-207/-202; AT-2，-154/-142;和AT-3，-88/-83）显示特异性结合β细胞衍生的MIN 6细胞中的核因子，其随后在免疫学上被鉴定为胰岛素基因转录因子PDX-1。当在MIN 6细胞中检测启动子活性时，AT-1或AT-3的破坏而不是AT-2的破坏引起IAPP基因启动子的显著减少。因此，尽管观察到所有三个A元件样区域可以与PDX-1结合，但AT-2位点可能不参与介导体内PDX-1作用。这些观察结果表明，PDX-1参与人类IAPP基因调控，这似乎是通过基因启动子中的至少两个A元件样顺式基序介导的。(C)1996学术出版社
The AT-rich eis-motif A elements of the insulin gene promoter contribute to directing the gene's expression to pancreatic beta-cells, bound by a homeodomin-containing transcription factor, PDX-1/IPF1/STF-1/IDX-1. The islet amyloid polypeptide (IAPP; amylin) gene, which is also expressed in limited tissues such as pancreatic beta- and delta-cells, contained similar AT-rich sequences in its regulatory sequences. To understand the molecular basis of IAPP gene regulation, we evaluated the possible physiological significance of the motif in human IAPP gene regulation. All of the three typical A element-like sequences that matched the CT-box consensus (AT-1, -207/-202; AT-2, -154/-142; and AT-3, -88/-83) were shown to bind specifically to a nuclear factor in the beta-cell-derived MIN6 cells, which was subsequently identified immunologically as the insulin gene transcription factor PDX-1. When the promoter activity was examined in MIN6 cells, the disruption of AT-1 or AT-3 but not of AT-2 caused a marked reduction in the IAPP gene promoter. Thus, despite the observation that ll the three A element-like regions could bind to PDX-1, the AT-2 site may not be involved in mediating the PDX-1 action in vivo. These observations suggest the involvement of PDX-1 in human IAPP gene regulation, which seems to be mediated through at least two A element-like cis-motifs in the gene promoter. (C) 1996 Acamdemic Press