Bt. Spear, MOUSE ALPHA-FETOPROTEIN GENE 5' REGULATORY ELEMENTS ARE REQUIRED FOR POSTNATAL REGULATION BY RAF AND RIF, Molecular and cellular biology, 14(10), 1994, pp. 6497-6505
The mouse alpha-fetoprotein (AFP) gene is expressed at high levels in
the yolk sac and fetal liver and at low levels in the fetal gut. AFP s
ynthesis decreases dramatically shortly after birth to low levels that
are maintained in the adult liver and gut. AFP expression can be reac
tivated in the adult liver upon renewed cell proliferation such as dur
ing liver regeneration or in hepatocellular carcinomas. Previously, tw
o unlinked genetic loci that modulate postnatal AFP levels were identi
fied. The raf locus controls, at least in part, basal steady-state AFP
mRNA levels in adult liver. Rif influences the extent of AFP mRNA ind
uction during liver regeneration. Transgenic mice were used to examine
the role of 5' AFP regulatory regions in raf- and Rif-mediated contro
l. A fragment of the AFP 5' region containing enhancer element I, the
repressor, and the promoter was linked to the mouse class I H-2D(d) st
ructural gene. We demonstrate that this hybrid AFP-Dd transgene is exp
ressed in the appropriate tissues. In addition, it is postnatally repr
essed and reactivated during liver regeneration in parallel with the e
ndogenous AFP gene. Therefore, proper transcriptional control does not
require the AFP structural gene. Furthermore, the AFP 5' control regi
on is sufficient to confer raf and Rif responsiveness to the linked H-
2D(d) structural gene, suggesting that raf and Rif act at the level of
transcriptional initiation.