An alternative splice variant of the tissue specific transcription factor HNF4alpha predominates in undifferentiated murine cell types.
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.
Nakhei
H
H
Universitätsklinikum Essen, Institut für Zellbiologie (Tumorforschung), Hufelandstrasse 55, D-45122 Essen, Germany.
Lingott
A
A
Lemm
I
I
Ryffel
G U
GU
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins; D054278:Embryonal Carcinoma Stem Cells; D005091:Exons; D015870:Gene Expression; D014644:Genetic Variation; D005938:Glucocorticoids / Q000494:pharmacology; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009928:Organ Specificity; D010750:Phosphoproteins / Q000032:analysis* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; C501970:Tcfl4 protein, mouse; D014157:Transcription Factors