Dk. Peyton et al., Position-dependent activity of alpha-fetoprotein enhancer element III in the adult liver is due to negative regulation, P NAS US, 97(20), 2000, pp. 10890-10894
Citations number
36
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
alpha-Fetoprotein (AFP) transcription is activated early in hepatogenesis.
but is dramatically repressed within several weeks after birth. AFP regulat
ion is governed by multiple elements including three enhancers termed EI. E
II, and EIII. All three AFP enhancers continue to be active in the adult li
ver, where EI and EII exhibit high levels of activity in pericentral hepato
cytes with a gradual reduction in activity in a pericentral-periportal dire
ction. In contrast to these two enhancers, EIII activity is highly restrict
ed to a layer of cells surrounding the central veins. To test models that c
ould account for position-dependent EIII activity in the adult liver, we ha
ve analyzed transgenes in which AFP enhancers EII and EIII were linked toge
ther. our results indicate that the activity of EIII is dominant over that
of EII, indicating that EIII is a potent negative regulatory element in all
hepatocytes except those encircling the central veins. We have localized t
his negative activity to a 340-bp fragment. This suggests that enhancer III
may be involved in postnatal AFP repression.