AN ALTERNATIVE SPLICE VARIANT OF THE TISSUE-SPECIFIC TRANSCRIPTION FACTOR HNF4-ALPHA PREDOMINATES IN UNDIFFERENTIATED MURINE CELL-TYPES

The transcription factor hepatocyte nuclear factor 4 alpha (HNF4 alpha ) is a tissue specific transcription factor mainly expressed in the li ver, kidney, intestine and the endocrine pancreas, but is also an esse ntial regulator for early embryonic events, Based on its protein struc ture HNF4 alpha. is classified as an orphan member of the nuclear rece ptor superfamily, Comparing HNF4 alpha transcription factors in the di fferentiated and dedifferentiated murine hepatocyte cell line MHSV-12 we identified in dedifferentiated cells the novel splice variant HNF4 alpha 7, This variant is characterized by an alternative first exon an d has a lower transactivation potential in transient transfection assa ys using HNF4 dependent reporter genes, HNF4 alpha 7 mRNA and the corr esponding protein are expressed in the undifferentiated pluripotent em bryonal carcinoma cell line F9, whereas HNF4 alpha 1 only appears afte r differentiation of F9 cells to visceral endoderm, HNF4 alpha 7 mRNA is also found in totipotent embryonic stem cells, However, the functio n of HNF4 alpha 7 seems not to be restricted to embryonic cells as the HNF4 alpha 7 mRNA is also present in adult tissues, most notably the stomach, All these features suggest that the presence of distinct spli ce variants of HNF4 alpha modulates the activity of HNF4 alpha in a ce ll type specific way.