RGD Reference Report - Functions of HNF1 family members in differentiation of the visceral endoderm cell lineage. - Rat Genome Database

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Functions of HNF1 family members in differentiation of the visceral endoderm cell lineage.

Authors: Haumaitre, C  Reber, M  Cereghini, S 
Citation: Haumaitre C, etal., J Biol Chem. 2003 Oct 17;278(42):40933-42. Epub 2003 Jul 14.
RGD ID: 1599302
Pubmed: PMID:12860991   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M304372200   (Journal Full-text)

The two members of the hepatocyte nuclear factor 1 (HNF1) transcription factor family, HNF1 and variant HNF1 (vHNF1), show a strong homology in their atypical POU-homeodomain and dimerization domain but differ in their transactivation domains. Moreover, two vHNF1 isoforms generated by alternative splicing are present in all tissues expressing this gene. vHnf1-deficient mouse embryos die soon after implantation due to defective visceral endoderm formation, an extraembryonic tissue essential for development and survival of the embryo proper. In contrast, invalidation of Hnf1, which is expressed at later developmental stages than vHnf1, does not lead to embryonic lethality or developmental defects. To examine the specific or potential equivalent functions of vHNF1 isoforms and HNF1 during the process of visceral endoderm differentiation, we stably reexpressed these factors in vHnf1-deficient embryonic stem cells. Analysis of these embryonic stem cells upon differentiation into embryoid bodies shows that vHNF1 isoforms exhibit specific behaviors depending on particular target genes and cooperate in the establishment of a functional visceral endoderm. Furthermore, forced expression of HNF1 in vHnf1-deficient embryonic stem cells fully restores the formation of a mature visceral endoderm with the correct expression profile of early and late markers of this lineage. Thus, in this context, HNF1 functionally replaces both vHNF1 isoforms, suggesting that the different developmental functions of these transcription factors are mainly due to the acquisition of novel expression patterns.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
embryonic morphogenesis  IDA 1599302 RGD 
positive regulation of transcription by RNA polymerase II  IDA 1599302 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
DNA-binding transcription factor activity, RNA polymerase II-specific  IDA 1599302 RGD 
sequence-specific DNA binding  IDA 1599302 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hnf1b  (HNF1 homeobox B)

Objects referenced in this article
Gene Hnf1b HNF1 homeobox B Mus musculus

Additional Information