Hepatocyte nuclear factor 3beta (Foxa2) is dispensable for maintaining the differentiated state of the adult hepatocyte.

Sund NJ, Ang SL, Sackett SD, Shen W, Daigle N, Magnuson MA, Kaestner KH
Mol Cell Biol. 2000 20 (14): 5175-83

PMID: 10866673 · PMCID: PMC85966 · DOI:10.1128/mcb.20.14.5175-5183.2000

Liver-specific gene expression is controlled by a heterogeneous group of hepatocyte-enriched transcription factors. One of these, the winged helix transcription factor hepatocyte nuclear factor 3beta (HNF3beta or Foxa2) is essential for multiple stages of embryonic development. Recently, HNF3beta has been shown to be an important regulator of other hepatocyte-enriched transcription factors as well as the expression of liver-specific structural genes. We have addressed the role of HNF3beta in maintenance of the hepatocyte phenotype by inactivation of HNF3beta in the liver. Remarkably, adult mice lacking HNF3beta expression specifically in hepatocytes are viable, with histologically normal livers and normal liver function. Moreover, analysis of >8,000 mRNAs by array hybridization revealed that lack of HNF3beta affects the expression of only very few genes. Based on earlier work it appears that HNF3beta plays a critical role in early liver development; however, our studies demonstrate that HNF3beta is not required for maintenance of the adult hepatocyte or for normal liver function. This is the first example of such functional dichotomy for a tissue specification transcription factor.

MeSH Terms (22)

Age Factors Animals Cell Differentiation DNA-Binding Proteins Female Gene Expression Profiling Gene Expression Regulation, Developmental Gene Silencing Glucose Hepatocyte Nuclear Factor 3-beta Homeostasis Integrases Liver Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Nuclear Proteins Transcription, Genetic Transcription Factors Viral Proteins

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