Numerous liver specific genes are transcriptionally activated by the binding to their promoter or enhancer of Hepatic Nuclear Factor 1 (HNF1). HNF1 contains a variant homeo-domain and binds to DNA as either a homodimer or a heterodimer with the vHNF1 protein. Surprisingly, HNF1 is not restricted to hepatocytes but is expressed in epithelial cells of several endoderm derived organs and in mesoderm derived kidney tubules. Hence, HNF1 alone can not account for the differentiated state of the hepatic cells. In fact, several other liver-enriched transcription factors have been cloned. The hepatic phenotype could result from the combinatorial expression of these regulators. Possible involvement of these trans-acting factors in liver organogenesis and hepatic differentiation is discussed.