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PMID: 8101632 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The distal enhancer implicated in the developmental regulation of the tyrosine aminotransferase gene is bound by liver-specific and ubiquitous factors.

Molecular and cellular biology ·Vol. 13 ·No. 8 ·1993-08-00 ·Pages 4494-504

Nitsch D, Schütz G

Abstract

Tyrosine aminotransferase gene expression is confined to parenchymal cells of the liver, is inducible by glucocorticoids and glucagon, and is repressed by insulin. Three enhancers control this tissue-specific and hormone-dependent activity, one of which, located at -11 kb, is implicated in establishing an active expression domain. We have studied in detail this important regulatory element and have identified a 221-bp fragment containing critical enhancer sequences which stimulated the heterologous thymidine kinase promoter more than 100-fold in hepatoma cells. Within this region, we have characterized two essential liver-specific enhancer domains, one of which was bound by proteins of the hepatocyte nuclear factor 3 (HNF3) family. Analyses with the dedifferentiated hepatoma cell line HTC suggested that HNF3 alpha and/or -gamma, but not HNF3 beta, are involved in activating the tyrosine aminotransferase gene via the -11-kb enhancer. Genomic footprinting and in vitro protein-DNA binding studies documented cell-type-specific binding of ubiquitous factors to the second essential enhancer domain, which by itself stimulated the thymidine kinase promoter preferentially in hepatoma cells. These results will allow further characterization of the role of these enhancer sequences in developmental activation of the tyrosine aminotransferase gene.

Related Genes
TAT
MeSH Terms
Animals Base Sequence Cell Line DNA Mutational Analysis DNA-Binding Proteins/metabolism Enhancer Elements, Genetic Gene Expression Regulation, Enzymologic Hepatocyte Nuclear Factor 3-alpha Hepatocyte Nuclear Factor 3-beta Liver/enzymology Liver Neoplasms/genetics Liver Neoplasms, Experimental/genetics Molecular Sequence Data Nuclear Proteins/metabolism Oligodeoxyribonucleotides/chemistry Point Mutation Rats Regulatory Sequences, Nucleic Acid Restriction Mapping Sequence Deletion Transcription Factors Tyrosine Transaminase/genetics
Chemicals
DNA-Binding Proteins Foxa1 protein, rat Foxa2 protein, rat Hepatocyte Nuclear Factor 3-alpha Nuclear Proteins Oligodeoxyribonucleotides Transcription Factors Hepatocyte Nuclear Factor 3-beta Tyrosine Transaminase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Nitsch D
Division Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg.
Schütz G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.8.4494-4504.1993
Published
1993-08-00
Pages
4494-504
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360060
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.13.8.4494-4504.1993 PMC Full Text View journal details
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