Nahon J L, Tratner I, Poliard A, Presse F, Poiret M, Gal A, Sala-Trepat J M, Legrès L, Feldmann G, Bernuau D
Laboratoire d'Enzymologie, Centre National de la Recherche Scientifique, Gif-sur- Yvette, France.
J Biol Chem. 1988 Aug 15;263(23):11436-42.
Albumin and alpha-fetoprotein (AFP), two major serum proteins, are synthesized predominantly in the liver and yolk sac of mammals. In the present paper we report on the developmental expression of the corresponding genes in nonhepatic rat tissues. Significant quantities of mature albumin and AFP mRNAs were revealed in kidney, pancreas, heart, and lung of fetal and/or newborn rats using dot blot and Northern blot assays. Very low levels of these mRNA sequences were also detected in adult kidney and pancreas using sensitive RNA-cDNA solution hybridization assays. In situ hybridization analysis revealed that the albumin and AFP gene transcripts are present in the tubular cells of the 20-day-old fetal kidney. In order to elucidate further the mechanisms governing this expression, we studied the chromatin structure and methylation pattern in the 5'-end of these two genes. A faint band, corresponding to a specific DNase I-hypersensitive site upstream from the albumin gene, was detected in the fetal and neonatal kidney nuclei but not in adult kidney. For both genes, a site CG, demethylation of which is correlated with expression in liver and hepatoma cell lines, is highly methylated in fetal kidney even though AFP and albumin genes are expressed. Taken together, these results show the presence of a cell population in the rat kidney that actively transcribes both the albumin and AFP genes. The expression of these genes may be mediated by mechanisms differing in at least some steps from those exerted in the liver.
白蛋白和甲胎蛋白（AFP）是两种主要的血清蛋白，主要在哺乳动物的肝脏和卵黄囊中合成。在本文中，我们报道了相应基因在大鼠非肝脏组织中的发育表达情况。使用斑点印迹法和Northern印迹法在胎鼠和/或新生鼠的肾脏、胰腺、心脏和肺中检测到了大量成熟的白蛋白和AFP mRNA。使用灵敏的RNA - cDNA溶液杂交法在成年大鼠的肾脏和胰腺中也检测到了极低水平的这些mRNA序列。原位杂交分析显示，20日龄胎鼠肾脏的肾小管细胞中存在白蛋白和AFP基因转录本。为了进一步阐明调控这种表达的机制，我们研究了这两个基因5'端的染色质结构和甲基化模式。在胎鼠和新生鼠的肾脏细胞核中检测到一条微弱的条带，对应于白蛋白基因上游的一个特定的DNase I超敏位点，而在成年大鼠肾脏中未检测到。对于这两个基因，一个CG位点在胎鼠肾脏中高度甲基化，尽管AFP和白蛋白基因在表达，但该位点的去甲基化与肝脏和肝癌细胞系中的表达相关。综上所述，这些结果表明大鼠肾脏中存在一个细胞群体，该群体可活跃地转录白蛋白和AFP基因。这些基因的表达可能由至少在某些步骤上与肝脏中发挥作用的机制不同的机制介导。
