Differential regulation of hepatocyte-enriched transcription factors explains changes in albumin and transthyretin gene expression among hepatoma cells.
To investigate the regulation of genes whose expression is enriched in liver we studied expression of the albumin and transthyretin (TTR) genes in a series of rat hepatoma cell lines (FaO, C2, C2rev7, and H5) that express these genes at different rates. The level of expression of albumin and TTR was compared to the expression and DNA-binding activity of four transcription factors, HNF1/LFB1, C/EBP, HNF3, and HNF4, that are found at high concentrations in liver. We conclude that the levels of these factors are controlled both transcriptionally (HNF-3, HNF-4, and C/EBP) and post-transcriptionally (HNF-1/LFB1), and that the cellular concentration of these DNA-binding proteins helps explain the level of transcriptional activity observed for the genes they regulate.
Herbst
R S
RS
Rockefeller University, New York, NY 10021.
Nielsch
U
U
Sladek
F
F
Lai
E
E
Babiss
L E
LE
Darnell
J E
JE
D000418:Albumins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D051543:Hepatocyte Nuclear Factor 3-gamma; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009841:Oligonucleotides; D010750:Phosphoproteins; D011228:Prealbumin / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000418:Albumins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C496501:Foxa1 protein, rat; C496504:Foxa2 protein, rat; C496507:Foxa3 protein, rat; D051538:Hepatocyte Nuclear Factor 1-alpha; D051541:Hepatocyte Nuclear Factor 3-alpha; D051557:Hepatocyte Nuclear Factor 4; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D009841:Oligonucleotides; D010750:Phosphoproteins; D011228:Prealbumin; D012333:RNA, Messenger; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051543:Hepatocyte Nuclear Factor 3-gamma; D051542:Hepatocyte Nuclear Factor 3-beta; D051539:Hepatocyte Nuclear Factor 1-beta; D004247:DNA