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Nucleic Acids Research, 1992, Vol. 20, No. 20 5321-5328
© 1992

MOLECULAR BIOLOGY

Trans-dominant inhibition of transcription activator LFB1

Alfredo Nicosia, Tafi Rosalba and Paolo Monaci*

IRBM, Istituto di Ricerche di Biologia Molecolare ‘P.Angeletti’, Via Pontina Km 30.600, 00040 Pomezia, Rome, Italy

* To whom correspondence should be addressed

Received July 23, 1992. Revised September 25, 1992. Accepted September 25, 1992.

Liver-enriched factor LFB1 (also named HNF1) is a dimeric transcription activator which is essential for the expression of many hepatocyte-speciflc genes. Here we demonstrate that LFB1 mutants in the POU A-like or in the homeo domains inhibit wild-type DNA binding by forming inactive heterodimeric complexes. Cotransfection of one of these mutants with wild-type LFB1 in HeLa cells eliminated LFB1 DNA binding and transcriptlonal activities through a trans-dominant mechanism. Expression of the same dominant negative mutant in human hepatoma HepG2 cells only partially Inhibited endogenous LFB1 activity, due to stabilization of LFB1 dimers in these cells. Dimer stabilization in hepatoma cells is mediated by a heat-labile association with an 11kD polypeptide, analogous to the DCoH cofactor identified in rat liver by Mendel et al. (1). The property of stabilizing LFB1 dimers is also shared by HeLa cells which produce a HeLa homolog of DCoH. These results demonstrate that LFB1 dlmer stabilization as well as the synthesis of ‘stabilizing factors’ are not restricted to cells expressing LFB1 or other members of its family.


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