Regulation of the human ascorbate transporter SVCT2 exon 1b gene by zinc-finger transcription factors.
Regulation of the human ascorbate transporter SVCT2 exon 1b gene by zinc-finger transcription factors.
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DOI：
10.1016/j.freeradbiomed.2011.02.006
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发表时间：
2011-05-01
影响因子：
7.4
通讯作者：
May, James M.
中科院分区：
文献类型：
--
作者：
Qiao, Huan;May, James M.
钠依赖性维生素C转运蛋白（SVCT）2对于代谢活性和专门组织中的抗坏血酸摄取至关重要。目前的研究集中在SVCT 2外显子1b的基因调控，这是普遍表达在人类和小鼠组织。虽然人SVCT 2外显子1b启动子不包含经典的TATA盒，但我们发现它确实包含一个功能性起始子（Inr），该起始子结合YY 1并与近端启动子区的上游Sp1/Sp3元件相互作用。这些元件反过来又在调控YY 1介导的外显子1b基因转录中发挥关键作用。启动子上YY 1/Sp复合物的形成是其任选功能所必需的。YY 1与Sp1或Sp3协同增强外显子1b启动子活性以及内源性SVCT 2蛋白表达。此外，除了Sp1/Sp3之外，在结合具有EGR/WT 1和Sp1/3的重叠结合位点的三个GC盒的蛋白质复合物中检测到EGR-1和EGR-2。EGR家族因子，WT 1和MAZ被发现差异调节外显子1b启动子活性。这些结果表明，SVCT 2外显子1b启动子中富含GC的共有序列上转录因子的差异占据有助于调节SVCT 2的细胞和组织表达。
The sodium-dependent vitamin C transporter (SVCT) 2 is crucial for ascorbate uptake in metabolically active and specialized tissues. The present study focused on the gene regulation of the SVCT2 exon 1b, which is ubiquitously expressed in human and mouse tissues. Although the human SVCT2 exon 1b promoter doesn’t contain a classical TATA-box, we found that it does contain a functional initiator (Inr) that binds YY1 and interacts with upstream Sp1/Sp3 elements in the proximal promoter region. These elements in turn play a critical role in regulating YY1-mediated transcription of the exon 1b gene. Formation of YY1/Sp complexes on the promoter is required for its optional function. YY1 with Sp1 or Sp3 synergistically enhanced exon 1b promoter activity as well as the endogenous SVCT2 protein expression. Further, in addition to Sp1/Sp3 both EGR-1 and -2 were detected in the protein complexes that bound the three GC boxes bearing overlapping binding sites for EGR/WT1 and Sp1/3. The EGR family factors, WT1 and MAZ were found to differentially regulate exon 1b promoter activity. These results show that differential occupancy of transcription factors on the GC-rich consensus sequences in SVCT2 exon 1b promoter contributes to the regulation of cell and tissue expression of SVCT2.
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影响因子：
64.5
作者：
COUREY, AJ;TJIAN, R
通讯作者：
TJIAN, R
影响因子：
4.3
作者：
Best, KA;Holmes, ME;Grover, AK
通讯作者：
Grover, AK
DOI：
10.1016/s0167-4781(98)00151-1
发表时间：
1998-11-08
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Faaland, CA;Race, JE;Holtzman, EJ
通讯作者：
Holtzman, EJ
影响因子：
6.5
作者：
Kawada, H;Nishiyama, C;Ogawa, H
通讯作者：
Ogawa, H
DOI：
10.1046/j.1523-5408.2002.00005.x
发表时间：
2002-03-01
期刊：
Nutrition in clinical care : an official publication of Tufts University
影响因子：
--
作者：
Jacob, Robert A;Sotoudeh, Gity
通讯作者：
Sotoudeh, Gity