Griffo G, Hamon-Benais C, Angrand P O, Fox M, West L, Lecoq O, Povey S, Cassio D, Weiss M
Unité de Génétique de la Différenciation, URA Centre National de la Recherche Scientifique 1149, Institut Pasteur, Paris, France.
J Cell Biol. 1993 May;121(4):887-98. doi: 10.1083/jcb.121.4.887.
Rat hepatoma-human fibroblast hybrids of two independent lineages containing only 8-11 human chromosomes show pleiotropic extinction of thirteen out of fifteen hepatic functions examined. Reexpression of the entire group of functions most often occurs in a block, and except for one discordant subclone, correlates with loss of human chromosome 2. The extinguished cells and their reexpressing derivatives have been examined for the expression of seven liver-enriched transcription factors. C/EBP, LAP, DBP, HNF3, and vHNF1 expression are not systematically extinguished in parallel with the hepatic functions. However, HNF1 and HNF4 show a perfect correlation with phenotype: these factors are expressed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be proposed that the HNF4 gene is the primary target of the pleiotropic extinguisher.
两个独立谱系的大鼠肝癌-人成纤维细胞杂种，仅含8 - 11条人类染色体，在所检测的15种肝功能中，有13种出现多效性功能丧失。整组功能的重新表达通常以整体形式出现，除了一个不一致的亚克隆外，这与人类2号染色体的丢失相关。对功能丧失的细胞及其重新表达的衍生物进行了七种肝脏富集转录因子表达的检测。C/EBP、LAP、DBP、HNF3和vHNF1的表达与肝功能丧失并非平行系统性地消失。然而，HNF1和HNF4与表型呈现完美的相关性：这些因子仅在显示多效性重新表达的细胞中表达。由于最近的证据表明HNF4控制HNF1的表达，因此可以提出HNF4基因是多效性功能丧失的主要靶点。
