Two genetically defined trans-acting loci coordinately regulate overlapping sets of liver-specific genes

Area of Science:

• Molecular Biology
• Developmental Biology
• Genetics

Background:

• Mice with deletions near the albino locus exhibit a lethal neonatal phenotype.
• This phenotype is linked to the loss of a trans-acting factor, alf.
• Neonatal liver functions are impaired in alf-deficient mice.

Purpose of the Study:

• To identify genes regulated by the alf trans-acting factor.
• To investigate the role of glucocorticoids and cAMP in alf-mediated gene expression.
• To explore the interaction between alf and the tissue-specific extinguisher locus Tse-1.

Main Methods:

• Differential cDNA screening to isolate alf-responsive genes.
• Analysis of gene expression patterns in response to hormonal stimuli.
• Investigating the effect of Tse-1 on alf-regulated genes.

Main Results:

• Identified genes whose transcription is affected by alf.
• Found that alf-responsive genes are induced by glucocorticoids and cAMP.
• Discovered that Tse-1 negatively controls a subset of alf-responsive genes.
• Demonstrated that glucocorticoids and cAMP can overcome Tse-1-mediated repression.

Conclusions:

• Two trans-acting factors, alf and Tse-1, coordinate the regulation of overlapping liver-specific gene sets.
• The lethal phenotype and extinguished gene expression likely result from disruptions in hormone signal transduction pathways.