Orphan Nuclear Receptor HNF-4 Binds to the Human Coagulation Factor VII Promoter (*)
Orphan Nuclear Receptor HNF-4 Binds to the Human Coagulation Factor VII Promoter (*)
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孤儿核受体 HNF-4 与人凝血因子 VII 启动子结合 (*)
DOI：
--
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发表时间：
1995
影响因子：
4.8
通讯作者：
J. Heim
中科院分区：
文献类型：
--
作者：
D. Erdmann;J. Heim
人凝血蛋白酶因子VII在凝血级联的启动过程中，无论是外在途径还是内在途径，都起着举足轻重的作用。虽然编码因子VII的基因主要在肝脏中表达，但这种组织特异性表达的机制尚未阐明。在本研究中，我们分析了ATG翻译起始密码子上游5千碱基对肝因子VII基因转录的贡献。在肝脏和非肝脏细胞系HepG2和HeLa中进行的一组嵌套缺失的瞬时转染实验表明，有几个区域参与了肝脏特异性表达。在HepG2细胞中，- 1212上游的序列介导了对因子VII启动子活性的轻微负面影响。DNase I保护实验揭示了近714个碱基对中的6个足迹，FPVII1至FPVII6，但仅包含FPVII3-6的165个碱基对的最小启动子足以在HepG2细胞中获得肝脏特异性表达。有趣的是，位于传感链- 14至+10位置的FPVII6表明，ATG翻译起始密码子有一个未知的转录因子覆盖。凝胶阻滞实验表明，富集肝脏的转录因子HNF-4在- 71至- 49位特异性结合到足迹FPVII4上。此外，将因子IX的HNF-4结合位点的T - a翻转引入因子VII的HNF-4结合位点，使启动子活性降低了20-50%。协调hnf -4介导的几种血液蛋白酶基因以及参与脂质代谢的基因的调节可能解释了这些因素与闭塞性心脏病风险增加的正相关。
The human coagulation protease factor VII plays a pivotal role in the initiation of the coagulation cascade by both the extrinsic and the intrinsic pathway. Although the gene, encoding factor VII, is expressed predominantly in the liver, the mechanisms underlying this tissue-specific expression have not been elucidated. In this study, we have analyzed the contribution of 5 kilobases upstream of the ATG translational initiation codon upon hepatic factor VII gene transcription. Transient transfection assays of a set of nested deletions in both liver and non-liver cell lines, HepG2 and HeLa respectively, indicate that several regions are involved in liver-specific expression. A slight negative effect on factor VII promoter activity in HepG2 cells is mediated by sequences upstream of position −1212. DNase I protection experiments reveal six footprints, FPVII1 through FPVII6, within the proximal 714 base pairs but a minimal promoter of 165 base pairs containing only FPVII3-6 is sufficient to confer liver-specific expression in HepG2 cells. Interestingly, FPVII6, at position −14 to +10 on the sense strand, would indicate that an as yet unknown transcription factor covers the ATG translational initiation codon. Gel retardation experiments show that the liver-enriched transcription factor HNF-4 binds specifically to footprint FPVII4 at position −71 to −49. Furthermore, a T A transversion, that in the HNF-4 binding site of factor IX causes a severe bleeding disorder, was introduced into the HNF-4-binding site of factor VII and reduced promoter activity by 20-50%. Coordinate HNF-4-mediated regulation of several blood protease genes as well as genes involved in lipid metabolism might account for the positive correlation of these factors with increased risk of occlusive heart diseases.
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DOI：
10.1016/s0021-9258(19)49613-0
发表时间：
1992-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Ladias;M. Hadzopoulou-Cladaras;D. Kardassis;P. Cardot;Jian Cheng;V. Zannis;C. Cladaras;John A. A.
通讯作者：
J. Ladias;M. Hadzopoulou-Cladaras;D. Kardassis;P. Cardot;Jian Cheng;V. Zannis;C. Cladaras;John A. A.
人类凝血酶原编码基因富含 Alu 的 5 侧翼区域的表征：调节肝脏特异性表达的正顺式作用元件的鉴定。
影响因子：
3.5
作者：
Bancroft,JD;Schaefer,LA;Degen,SJ
通讯作者：
Degen,SJ
人 ApoA-II 基因肝转录所需的启动子元件和因子。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chambaz,J;Cardot,P;Pastier,D;Zannis,VI;Cladaras,C
通讯作者：
Cladaras,C
人因子 IX 基因的调节机制：Leyden 特异性区域的蛋白质结合。
影响因子：
2.9
作者：
Kurachi,S;Furukawa,M;Salier,JP;Wu,CT;Wilson,EJ;French,FS;Kurachi,K
通讯作者：
Kurachi,K
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Huang,MN;Hung,HL;Stanfield-Oakley,SA;High,KA
通讯作者：
High,KA