Species differences in the regulation mechanisms between human and mouse carboxylesterase genes

哺乳动物羧酸酯酶（CES）是一个多基因家族，其基因产物定位于内质网。我们最近描述了人肝脏中CES的主要形式，称为CES HU 1，属于CES 1家族，并且认为它在药物和脂质代谢中起重要作用。由于CES HU 1的表达水平可能影响脂肪和脂质的水平，因此了解CES HU 1基因表达的调节机制非常重要。在本研究中，我们分离了两个编码人CES HU 1的CES基因，暂命名为CES HU 1a和CES HU 1b。这两个基因都存在于16号染色体上的反向重复中。这些基因是完全相似的，除了外显子1和推定的顺式元件。在人肝脏中，CES HU 1a的转录水平远高于CES HU 1b。缺失分析和电泳迁移率变动分析结果表明，-160 ~+54区域由两个基因启动子组成。然而，Sp1和GEBP与CES HU 1a启动子相互作用，而不是CES HU 1b启动子。得出的结论是，这两个基因最有可能产生于早期的基因复制事件，它们的高度保守的结构和在转录水平上的调节差异有力地证明了每个基因产物在细胞代谢中的重要作用。

Mammalian carboxylesterase (CES) comprise a multigene family, which gene products are localized in the endoplasmic reticulum. We have recently described that major forms of CES in the human liver termed CES HU1 belongs to the CES1 family and that it is thought to play an important roles in drug and lipid metabolism. Since the expression level of CES HU1 may affect the level of chugs and lipid, it is important to understand the mechanism by which CES HU1 gene expression is regulated. In this study, we isolated the two CES genes encoding human CES HU1, which were tentatively designated as CES HU1a and CES HU1b. Both genes exist in inverted duplication on chromosome 16. These genes were completely similar, except for exon 1 and putative cis elements. The transcriptional level of CES HU1a was much higher than CES HU1b in human livers. Results of deletion assays and electrophoretic mobility shift assays suggested that the region from -160 to +54 consisted of the both gene promoters. However, Sp1 and GEBP interacted with the CES HU1a promoter, but not CES HU1b promoter. It was concluded that these two genes most probably arose from an early gene duplication event and that their highly conserved structures and difference in regulation at the transcriptional level argue strongly for a significant role for each gene product in cellular metabolism.