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Molecular Basis for the Hormonal Regulation of the Tyrosine Aminotransferase and Tryptophan Oxygenase Genes
Author(s) -
SCHÜTZ GÜNTHER,
SCHMID WOLFGANG,
JANTZEN MICHAEL,
DANESCH ULRICH,
GLOSS BERND,
STRÄHLE UWE,
BECKER PETER,
BOSHART MICHAEL
Publication year - 1986
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1986.tb15523.x
Subject(s) - german , library science , political science , biology , physiology , philosophy , linguistics , computer science
A classical example for hormonal control of gene expression is the induction of the enzymes tyrosine aminotransferase (TAT) and tryptophan oxygenase (TO).1-3 These two enzymes are expressed exclusively in the parenchymal cells of the liver.4 The expression ofboth genes is affected by glucocorticoids.slO In nuclear run-on assays it could be shown that hormonal induction involves changes in the relative rates of transcription of these two genes. Apart from glucocorticoid induction, the activity of the TAT gene is also regulated by cAMP."-14 The accumulation ofTAT mRNA after cAMP stimulation is a consequence of transcriptional activation of the TAT gene. Combined dexamethasone and cAMP treatment leads to higher TAT mRNA concentrations than treatment with either inducer alone, which implies that dexamethasone and cAMP act by distinct mechanisms. IS In addition to hormonal regulation, both TAT and TO genes are under developmental control. Whereas TAT enzyme activity appears around birth, TO enzyme activity can be detected only 2 weeks later.16 The activity of the TAT gene is affected by two distinct genetic loci, which appear to operate in trans on the expression of the TAT gene. By genetic and biochemical analysis of several albino lethai mutants of the mouse, a control region required for expression and inducibility of several liver enzymes including TAT has been assigned to the region of the albino locus on chromosome 7 of the mouse. l7 The basal level of TAT mRNA is severely decreased, and the concentration of the mRNA is no longer inducible by glucocorticoids and cAMP, aIthough the structural gene for TAT is still present. Because the mouse TAT structural gene is located on chromosome 8,'9 the effect of this presumptive regulatory locus must operate in trans. Another locus, the so-called tissue-specific extinguisher-l (Tse-l) has been mapped to chromosome 11 of the mouse. When chromosome 11 of a fibroblast cell is