Characterization of the distal alpha-fetoprotein enhancer, a strong, long distance, liver-specific activator.

Mouse F9 teratocarcinoma cells provide a system to study developmentally regulated alpha-fetoprotein (AFP) gene expression. AFP is not expressed in undifferentiated F9 cells but is induced when cells differentiate as cell aggregates in the presence of retinoic acid. Previous studies have led to the suggestion that undifferentiated F9 cells contain negative regulators of AFP expression. To test this, we have used transient heterokaryons to ask whether inactive AFP genes in undifferentiated F9 cells are responsive to positively acting trans-acting factors. Our results indicate that silent endogenous and transfected AFP genes are activated when undifferentiated F9 cells are fused to human hepatoma HepG2 cells. This suggests that the lack of AFP expression in undifferentiated F9 cells is due to the absence or insufficient level of positive-acting transcription factors, rather than the presence of dominant negative regulators. We also demonstrate that stably transfected AFP genes, although unmethylated, are properly regulated in F9 cells.

show abstract

Endogenous and transfected mouse alpha-fetoprotein genes in undifferentiated F9 cells are activated in transient heterokaryons

Spear

Ellis

1995

Somat Cell Mol Genet

View full text Add to dashboard Cite

show abstract

The Foxa family of transcription factors in development and metabolism

Friedman

Kaestner

2006

Cell. Mol. Life Sci.

440

378

View full text Add to dashboard Cite

The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors has been the subject of genetic and biochemical study for over 15 years. During this time its three members, Foxa1, Foxa2 and Foxa3, have been found to play important roles in multiple stages of mammalian life, beginning with early development, continuing during organogenesis, and finally in metabolism and homeostasis in the adult. Foxa2 is required for the formation of the node and notochord, and in its absence severe defects in gastrulation, neural tube patterning, and gut morphogenesis result in embryonic lethality. Foxa1 and Foxa2 cooperate to establish competence in foregut endoderm and are required for normal development of endoderm-derived organs such as the liver, pancreas, lungs, and prostate. In post-natal life, members of the Foxa family control glucose metabolism through the regulation of multiple target genes in the liver, pancreas, and adipose tissue. Insight into the unique molecular basis of Foxa function has been obtained from recent genetic and genomic data, which identify the Foxa proteins as 'pioneer factors' whose binding to promoters and enhancers enable chromatin access for other tissue-specific transcription factors.

show abstract

Transcriptional control in the mammalian liver: liver development, perinatal repression, and zonal gene regulation

Spear

Jin

Ramasamy

et al. 2006

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Liver function is crucial for maintaining metabolic homeostasis in mammals. Numerous genes must be properly regulated for the liver to develop and perform a variety of activities. Several recent gene-knockout studies in mice have clarified the roles of GATA6, HNF4alpha, and Foxa1/Foxa2 in early stages of liver formation. After the liver forms, transcriptional changes continue to occur; during the perinatal period, certain genes such as alpha-fetoprotein and H19 are silenced, others are activated, and position-dependent (or zonal) regulation is established. Zhx2 was recently identified as one factor involved in postnatal repression of alpha-fetoprotein and other genes. Furthermore, several studies indicate that negative regulation is involved in the zonal control of glutamine synthetase. Finally, exciting new evidence indicates that signaling through the Wnt/beta-catenin pathway is also involved in zonal regulation in the adult liver.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Characterization of the distal alpha-fetoprotein enhancer, a strong, long distance, liver-specific activator.

Cited by 31 publications

References 51 publications

Endogenous and transfected mouse alpha-fetoprotein genes in undifferentiated F9 cells are activated in transient heterokaryons

Endogenous and transfected mouse alpha-fetoprotein genes in undifferentiated F9 cells are activated in transient heterokaryons

The Foxa family of transcription factors in development and metabolism

Transcriptional control in the mammalian liver: liver development, perinatal repression, and zonal gene regulation

Contact Info

Product

Resources

About