Beale Elmus G, Forest Claude, Hammer Robert E
Department of Cell Biology and Biochemistry, School of Medicine, Stop 6540, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA.
Biochimie. 2003 Dec;85(12):1207-11. doi: 10.1016/j.biochi.2003.10.012.
Cytosolic phosphoenolpyruvate carboxykinase (EC 4.1.1.32; PEPCK-C) catalyzes the critical regulated step in adipocyte glyceroneogenesis. Numerous studies have shown that hormones and nutrients regulate PEPCK-C at the transcriptional level. We identified two upstream cis-acting DNA elements, gAF1/PCK1 and PCK2, that control adipocyte specific transcription of the PEPCK-C gene (Pck1). Both elements are direct repeat hexanucleotides separated by 1 bp (DR1 elements; variations of the sequence AGGTCAnAGGTCA). PCK2 is located 1 kbp upstream and is the essential element of an adipocyte specific enhancer. It is a peroxisome proliferator activated receptor gamma response element (PPRE) and directs the activation of the PEPCK-C gene during adipogenesis. In addition, it is a thiazolidinedione response element in mature adipocytes. In contrast, gAF1/PCK1, centered 445 bp upstream, is a pleiotropic element that mediates tissue specific glucocorticoid action-repression in adipocytes and induction in hepatocytes. It is a negative response element for PPARgamma, RXRalpha, COUP-TFII, and several unidentified proteins in some cell types, and a positive element for COUP-TFI and HNF4 in other cells type. The purpose of this presentation is to review the discovery and characterization of these two elements in adipocytes and describe how our work has contributed to understanding the mechanisms that control adipocyte glyceroneogenesis.
胞质磷酸烯醇式丙酮酸羧激酶（EC 4.1.1.32；PEPCK-C）催化脂肪细胞甘油生成过程中的关键调控步骤。大量研究表明，激素和营养物质在转录水平上调节PEPCK-C。我们鉴定出两个上游顺式作用DNA元件，即gAF1/PCK1和PCK2，它们控制PEPCK-C基因（Pck1）的脂肪细胞特异性转录。这两个元件都是由1个碱基对隔开的直接重复六核苷酸（DR1元件；序列AGGTCAnAGGTCA的变体）。PCK2位于上游1千碱基对处，是脂肪细胞特异性增强子的关键元件。它是过氧化物酶体增殖物激活受体γ反应元件（PPRE），在脂肪生成过程中指导PEPCK-C基因的激活。此外，它在成熟脂肪细胞中是噻唑烷二酮反应元件。相比之下，位于上游445碱基对处的gAF1/PCK1是一个多效性元件，介导脂肪细胞中组织特异性糖皮质激素作用的抑制以及肝细胞中的诱导作用。在某些细胞类型中，它是PPARγ、RXRα、COUP-TFII和几种未鉴定蛋白质的负反应元件，而在其他细胞类型中是COUP-TFI和HNF4的正反应元件。本报告的目的是回顾这两个元件在脂肪细胞中的发现和特征，并描述我们的工作如何有助于理解控制脂肪细胞甘油生成的机制。
