Regulation of the F11, Klkb1, Cyp4v3 gene cluster in livers of metabolically challenged mice.
Regulation of the F11, Klkb1, Cyp4v3 gene cluster in livers of metabolically challenged mice.
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DOI：
10.1371/journal.pone.0074637
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
van Vlijmen BJ
中科院分区：
文献类型：
--
作者：
Safdar H;Cleuren AC;Cheung KL;Gonzalez FJ;Vos HL;Inoue Y;Reitsma PH;van Vlijmen BJ
携带凝血因子XI（F11）、前激肽释放酶（KLKB 1）和细胞色素P450家族成员（CYP4V2）基因的4q35.2位点的单核苷酸多态性（SNP）与深静脉血栓形成（DVT）相关。这些SNP通过改变FXI的循环水平对DVT发挥作用。然而，与DVT相关的SNPs不一定都在F11中，KLKB 1和CYP4V2也有。在此，我们寻找F11基因外4q35.2基因座内可能控制FXI血浆水平和/或DVT风险的常见调控元件的证据。为此，我们研究了在几种影响小鼠肝脏F11转录的代谢条件下，小鼠基因簇的调节。在HNF 4 α（一种控制F11的关键转录因子）被siRNA消除或减少的小鼠肝脏中，观察到肝脏F11转录水平的强烈下降，这与Cyp4v3（CYP4V2的小鼠直向同源物）相关，但与Klkb 1水平无关。雌激素诱导肝F11和Cyp4v3，但不Klkb1转录水平，而甲状腺激素强烈诱导肝F11转录水平，并减少Cyp4v3，使Klkb1水平不受影响。喂食高脂饮食的小鼠也具有升高的F11转录，这明显受到Klkb1和Cyp4v3表达的诱导。我们的结论是，在小鼠F11，Klkb1，Cyp4v3基因簇，F11和Cyp4v3经常显示惊人的平行转录反应，这表明存在共享的调控元件。
Single nucleotide polymorphisms (SNPs) in a 4q35.2 locus that harbors the coagulation factor XI (F11), prekallikrein (KLKB1), and a cytochrome P450 family member (CYP4V2) genes are associated with deep venous thrombosis (DVT). These SNPs exert their effect on DVT by modifying the circulating levels of FXI. However, SNPs associated with DVT were not necessarily all in F11, but also in KLKB1 and CYP4V2. Here, we searched for evidence for common regulatory elements within the 4q35.2 locus, outside the F11 gene, that might control FXI plasma levels and/or DVT risk. To this end, we investigated the regulation of the orthologous mouse gene cluster under several metabolic conditions that impact mouse hepatic F11 transcription. In livers of mice in which HNF4α, a key transcription factor controlling F11, was ablated, or reduced by siRNA, a strong decrease in hepatic F11 transcript levels was observed that correlated with Cyp4v3 (mouse orthologue of CYP4V2), but not by Klkb1 levels. Estrogens induced hepatic F11 and Cyp4v3, but not Klkb1 transcript levels, whereas thyroid hormone strongly induced hepatic F11 transcript levels, and reduced Cyp4v3, leaving Klkb1 levels unaffected. Mice fed a high-fat diet also had elevated F11 transcription, markedly paralleled by an induction of Klkb1 and Cyp4v3 expression. We conclude that within the mouse F11, Klkb1, Cyp4v3 gene cluster, F11 and Cyp4v3 frequently display striking parallel transcriptional responses suggesting the presence of shared regulatory elements.
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影响因子：
5.3
作者：
Hayhurst, GP;Lee, YH;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
影响因子：
3.5
作者：
Selva, David M.;Hammond, Geoffrey L.
通讯作者：
Hammond, Geoffrey L.
DOI：
10.1016/s0162-3109(99)00069-7
发表时间：
1999-09-01
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Rojkjær, R;Schmaier, AH
通讯作者：
Schmaier, AH
影响因子：
6.5
作者：
Hanniman, Elyhisha A.;Lambert, Gilles;Sinal, Christopher J.
通讯作者：
Sinal, Christopher J.
影响因子：
3.7
作者：
Safdar H;Cheung KL;Vos HL;Gonzalez FJ;Reitsma PH;Inoue Y;van Vlijmen BJ
通讯作者：
van Vlijmen BJ