An alternative splice variant of the tissue specific transcription factor HNF4 predominates in undifferentiated murine cell types
Open Access
- 1 January 1998
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 26 (2) , 497-504
- https://doi.org/10.1093/nar/26.2.497
Abstract
The transcription factor hepatocyte nuclear factor 4α (HNF4α) 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 HNF4α is classified as an orphan member of the nuclear receptor superfamily. Comparing HNF4α transcription factors in the differentiated and dedifferentiated murine hepatocyte cell line MHSV-12 we identified in dedifferentiated cells the novel splice variant HNF4α7. This variant is characterized by an alternative first exon and has a lower transactivation potential in transient transfection assays using HNF4 dependent reporter genes. HNF4α7 mRNA and the corresponding protein are expressed in the undifferentiated pluripotent embryonal carcinoma cell line F9, whereas HNF4α1 only appears after differentiation of F9 cells to visceral endoderm. HNF4α7 mRNA is also found in totipotent embryonic stem cells. However, the function of HNF4α7 seems not to be restricted to embryonic cells as the HNF4α7 mRNA is also present in adult tissues, most notably the stomach. All these features suggest that the presence of distinct splice variants of HNF4α modulates the activity of HNF4α in a cell type specific way.Keywords
This publication has 42 references indexed in Scilit:
- Patterning the expression of a tissue-specific transcription factor in embryogenesis: HNF1α gene activation during Xenopus developmentMechanisms of Development, 1997
- Utilization of Recombinant Adenovirus and Dominant Negative Mutants to Characterize Hepatocyte Nuclear Factor 4-regulated Apolipoprotein AI and CIII ExpressionJournal of Biological Chemistry, 1997
- Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1)Nature, 1996
- Endoderm-Specific Gene Expression in Embryonic Stem Cells Differentiated to Embryoid BodiesExperimental Cell Research, 1996
- Transcriptional hierarchy in Xenopus embryogenesis: HNF4 a maternal factor involved in the developmental activation of the gene encoding the tissue specific transcription factor HNF1α (LFB1)Mechanisms of Development, 1996
- Estrogen‐Inducible Derivatives of Hepatocyte Nuclear Factor‐4, Hepatocyte Nuclear Factor‐3 and Liver Factor B1 are Differently Affected by Pure and Partial AntiestrogensEuropean Journal of Biochemistry, 1994
- Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liverGene, 1994
- The hepatocyte-specific phenotype of murine liver cells correlates with high expression of connexin32 and connexin26 but very low expression of connexin43Experimental Cell Research, 1992
- A transcriptional hierarchy involved in mammalian cell-type specificationNature, 1992
- Ubiquitous MyoD transcription at the midblastula transition precedes induction-dependent MyoD expression in presumptive mesoderm of X. laevisCell, 1991