Liver-enriched transcription factors and hepatocyte differentiation.
Liver-specific gene expression in adult hepatocytes relies on four families of evolutionary conserved transcription factors that are liver-enriched but not restricted to this tissue. These factors function in unique combinations, often synergistically, to stimulate cell-specific transcription. Each family is composed of several members displaying similar, if not identical, DNA recognition properties and sharing structural homology in their DNA binding domains. The homo- and heterodimerization between members of a particular transcription factor family adds an additional level of complexity in gene regulation. The consequences of inactivating different family members in the mouse by homologous recombination, together with recent studies of their regulation, suggest 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 developmental functions. Their possible role in the progression through different stages of hepatic cell commitment and differentiation is discussed.
Cereghini
S
S
Hôpital Necker Enfants Malades, Paris, France.
D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology; D004707:Endoderm / Q000502:physiology; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D051543:Hepatocyte Nuclear Factor 3-gamma; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008099:Liver / Q000166:cytology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C496499:FOXA1 protein, human; C496502:FOXA2 protein, human; C496505:FOXA3 protein, human; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051541:Hepatocyte Nuclear Factor 3-alpha; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; C501970:Tcfl4 protein, mouse; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051543:Hepatocyte Nuclear Factor 3-gamma; D051542:Hepatocyte Nuclear Factor 3-beta; D051539:Hepatocyte Nuclear Factor 1-beta