LIVER-ENRICHED TRANSCRIPTION FACTORS AND HEPATOCYTE DIFFERENTIATION

Liver-specific gene expression in adult hepatocytes relies on four fam ilies of evolutionary conserved transcription factors that are liver-e nriched but not restricted to this tissue, These factors function in u nique combinations, often synergistically, to stimulate cell-specific transcription, Each family is composed of several members displaying s imilar, if not identical, DNA recognition properties and sharing struc tural homology in their DNA binding domains, The homo- and heterodimer ization between members of a particular transcription factor family ad ds an additional level of complexity in gene regulation, The consequen ces of inactivating different family members in the mouse by homologou s recombination, together with recent studies of their regulation, sug gest a model for liver differentiation involving a regulatory network rather than a completely hierarchical genetic circuitry, These studies also indicate that individual regulators appear to serve multiple dev elopmental functions, Their possible role in the progression through d ifferent stages of hepatic cell commitment and differentiation is disc ussed.