Schoonjans K, Staels B, Devos P, Szpirer J, Szpirer C, Deeb S, Verhoeven G, Auwerx J
Laboratoire de Biologie des Régulations chez les Eucaryotes, UMR 134, CNRS, Nice, France.
FEBS Lett. 1993 Aug 23;329(1-2):89-95. doi: 10.1016/0014-5793(93)80200-e.
The molecular mechanism underlying the extinction of lipoprotein lipase (LPL) expression in rat liver during development was investigated. A mouse (BWTG3) and a rat (7777) hepatoma, both of which exhibit characteristics of fetal hepatocytes, were found to contain LPL mRNA, whereas the more differentiated human (Hep G2 and Hep 3B) or rat (Fa32) hepatoma cell lines did not. Somatic cell hybrids between LPL-producing hepatoma cells and non-LPL-producing cells, such as adult rat hepatocytes or fibroblasts, exhibited extinction of LPL gene expression. Assay of expression of nested deletions in the 5' regulatory sequences of the LPL gene in the Hep G2 cell line and in BWTG3 cells localized sequences involved in the suppression of LPL production to a region between -591 and -288 relative to the transcription initiation site. A site with sequence homology to a glucocorticoid responsive element (GRE) was shown not to play an important role in the extinction process. A novel transcription factor, termed RF-1-LPL, was shown to bind to an NF-1-like site in this region. In contrast to neonatal animals, in adult animals an additional protein complex (RF-2-LPL), was formed on the NF-1-like site, suggesting that this sequence might recruit a trans-acting factor involved in the extinction of LPL gene expression in adult rat liver.
研究了大鼠肝脏发育过程中脂蛋白脂肪酶（LPL）表达消失的分子机制。发现一种小鼠（BWTG3）和一种大鼠（7777）肝癌细胞，二者均表现出胎儿肝细胞的特征，含有LPL mRNA，而分化程度更高的人（Hep G2和Hep 3B）或大鼠（Fa32）肝癌细胞系则没有。产生LPL的肝癌细胞与不产生LPL的细胞（如成年大鼠肝细胞或成纤维细胞）之间的体细胞杂种表现出LPL基因表达的消失。对Hep G2细胞系和BWTG细胞中LPL基因5'调控序列的嵌套缺失表达进行分析，将参与抑制LPL产生的序列定位到相对于转录起始位点-591至-288之间区域。一个与糖皮质激素反应元件（GRE）具有序列同源性的位点在消失过程中未发挥重要作用。一种名为RF-1-LPL的新型转录因子被证明可结合该区域的一个类NF-1位点。与新生动物不同，成年动物在类NF-1位点上形成了一种额外的蛋白质复合物（RF-2-LPL），这表明该序列可能募集了一种参与成年大鼠肝脏LPL基因表达消失的反式作用因子。
