Nucleic Acids Research, Vol 26, Issue 2 497-504, Copyright © 1998 by Oxford University Press
H Nakhei, A Lingott, I Lemm and GU Ryffel
The transcription factor hepatocyte nuclear factor 4alpha (HNF4alpha) is a
tissue specific transcription factor mainly expressed in the liver, kidney,
intestine and the endocrine pancreas, but is also an essential regulator
for early embryonic events. Based on its protein structure HNF4alpha is
classified as an orphan member of the nuclear receptor superfamily.
Comparing HNF4alpha transcription factors in the differentiated and
dedifferentiated murine hepatocyte cell line MHSV-12 we identified in
dedifferentiated cells the novel splice variant HNF4alpha7. This variant is
characterized by an alternative first exon and has a lower transactivation
potential in transient transfection assays using HNF4 dependent reporter
genes. HNF4alpha7 mRNA and the corresponding protein are expressed in the
undifferentiated pluripotent embryonal carcinoma cell line F9, whereas
HNF4alpha1 only appears after differentiation of F9 cells to visceral
endoderm. HNF4alpha7 mRNA is also found in totipotent embryonic stem cells.
However, the function of HNF4alpha7 seems not to be restricted to embryonic
cells as the HNF4alpha7 mRNA is also present in adult tissues, most notably
the stomach. All these features suggest that the presence of distinct
splice variants of HNF4alpha modulates the activity of HNF4alphain a cell
type specific way.
ARTICLES
An alternative splice variant of the tissue specific transcription factor HNF4alpha predominates in undifferentiated murine cell types
Universitatsklinikum Essen, Institut fur Zellbiologie (Tumorforschung), Hufelandstrasse 55, D-45122 Essen, Germany.
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