RGD Reference Report - Regulation of alpha-fetoprotein expression by Nkx2.8. - Rat Genome Database

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Regulation of alpha-fetoprotein expression by Nkx2.8.

Authors: Kajiyama, Y  Tian, J  Locker, J 
Citation: Kajiyama Y, etal., Mol Cell Biol 2002 Sep;22(17):6122-30.
RGD ID: 1302328
Pubmed: PMID:12167706   (View Abstract at PubMed)
PMCID: PMC134004   (View Article at PubMed Central)

The alpha-fetoprotein (AFP) gene is an important model of developmental gene silencing and neoplastic gene reactivation. Nkx2.8 is a divergent homeodomain factor originally cloned through its binding to the promoter-coupling element (PCE), a regulatory region upstream of the AFP promoter that mediates stimulation by distant enhancers. Nkx2.8 is the only developmentally regulated factor that has been associated with AFP gene expression. Fetoprotein transcription factor, an orphan nuclear receptor, has also been shown to bind the PCE but is not developmentally regulated. The binding specificities of both families of transcription factor were determined, and overlapping sites for each were defined in the PCE. After modification of nuclear extract and gel shift analysis procedures, Nkx2.8 was identified in six AFP-positive cell lines. Transient-transfection analysis did not show transcriptional stimulation by Nkx2.8 or other active NK2 factors, which only interfered with gene expression. However, two sets of analysis demonstrated the relationship of Nkx2.8 to AFP expression: chromatin immunoprecipitation demonstrated that Nkx2.8 bound to the active AFP promoter, and antisense inhibition of Nkx2.8 mRNA translation selectively reduced expression of both the endogenous human AFP gene and transfected reporters containing the rat AFP promoter.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sequence-specific DNA binding  IDA 1302328 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nkx2-8  (NK2 homeobox 8)

Objects referenced in this article
Gene Afp alpha-fetoprotein Rattus norvegicus

Additional Information