Primary structure, chromosomal mapping, expression and transcriptional activity of murine hepatocyte nuclear factor 4γ

We demonstrate the presence of a new member of the orphan nuclear receptor hepatocyte nuclear factor 4 (HNF4) subfamily in mouse which is genetically distinct from the previously characterized mouse HNF4 alpha gene. The new member of the HNF4 subfamily shows highest amino acid identity, similar tissue distribution and syntenous chromosomal localization to the recently described human HNF4 gamma (NR2A2), we therefore classify it as mouse HNF4 gamma (mHNF4 gamma). A combination of RT-PCR and immunohistochemical analysis showed expression of mHNF4 gamma mRNA and protein in the endocrine pancreas, testes, kidney and gut. By co-transfection experiments, we show that mHNF4 gamma is able to activate transcription, acting through binding sites that have been previously characterized as HNF4 alpha binding sites. The presence of HNF gamma in human and mouse implies that a complex transcriptional network exists in higher vertebrates involving a number of HNF4 members with overlapping yet distinct function and tissue distribution. (C) 2000 Elsevier Science B.V. All rights reserved.