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PMID:9096351

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Citation

Lim, L, Zhou, H and Costa, RH (1997) The winged helix transcription factor HFH-4 is expressed during choroid plexus epithelial development in the mouse embryo. Proc. Natl. Acad. Sci. U.S.A. 94:3094-9

Abstract

Mammalian hepatocyte nuclear factor-3 (HNF-3) and the Drosophila homeotic gene fork head proteins are prototypes of an extensive family of cell-specific transcription factors that share homology in the winged helix DNA-binding domain. One of these mammalian family members, HNF-3/fork head homolog-4 (HFH-4), was isolated by PCR amplification of rodent brain cDNA and exhibits abundant expression in the adult bronchiolar epithelium. In this study, we performed in situ hybridization of stage-specific mouse embryos and report on a novel expression pattern of the HFH-4 gene in both the presumptive and differentiated choroid plexus epithelium, which is responsible for the synthesis and secretion of cerebrospinal fluid (CSF) proteins. We also showed that HFH-4 is a potent transcriptional activator in cotransfection assays and defined several protein sequences important for HFH-4 transcriptional activity. We used in vitro DNA-binding site selection with recombinant HFH-4 protein and determined that the HFH-4 protein recognizes the DNA consensus sequences HWDTGTTTGTTTA or KTTTGTTGTTKTW (where H is not G, W is A or T, D is not C, and K is G or T). We used this HFH-4 consensus to identify potential HFH-4 target genes in the choroid plexus epithelium and demonstrated that these promoter sequences bind to recombinant HFH-4 protein in electrophoretic mobility shift assays. Recombinant HFH-4 formed specific protein-DNA complexes with the promoter regions of the human prothrombin, beta amyloid precursor protein, alpha1-antichymotrypsin, cystic fibrosis transmembrane conductance regulator and rodent alpha2-macroglobulin, growth hormone receptors, and insulin-like growth factor II genes. Furthermore, we identified putative HFH-4 target genes in the bronchiolar epithelium including the clara cell secretory protein gene and the HNF-3alpha gene, a winged helix family member involved in the transcriptional regulation of genes in the bronchiolar epithelium. In support of these binding studies, cotransfection assays show that HFH-4 potentiates expression of the HNF-3alpha and clara cell secretory protein promoter regions.

Links

PubMed PMC20327

Keywords

Amino Acid Sequence; Animals; Bronchi/embryology; Bronchi/metabolism; Choroid Plexus/embryology; Choroid Plexus/metabolism; DNA-Binding Proteins/genetics; Epithelium/embryology; Epithelium/metabolism; Gene Expression Regulation, Developmental; Humans; Mice; Molecular Sequence Data; Transcription Factors/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FOXJ1

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FOXJ1

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001952)

Seeded From UniProt

complete

MOUSE:FOXJ1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FOXJ1

involved_in

GO:0007420: brain development

ECO:0000270: expression pattern evidence used in manual assertion

P

  • occurs_in:(CL:0000706)

Seeded From UniProt

complete

MOUSE:FOXJ1

involved_in

GO:0060429: epithelium development

ECO:0000270: expression pattern evidence used in manual assertion

P

  • occurs_in:(CL:0000706)

Seeded From UniProt

complete

HUMAN:FOXJ1

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FOXJ1

enables

GO:0000976: transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FOXJ1

involved_in

GO:0007420: brain development

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXJ1

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FOXJ1

involved_in

GO:0060428: lung epithelium development

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXJ1

involved_in

GO:0007420: brain development

ECO:0000270: expression pattern evidence used in manual assertion

P

occurs_in:(CL:0000706)

Seeded From UniProt

complete

MOUSE:FOXJ1

involved_in

GO:0060429: epithelium development

ECO:0000270: expression pattern evidence used in manual assertion

P

occurs_in:(CL:0000706)

Seeded From UniProt

complete

MOUSE:FOXJ1

enables

GO:0000978: RNA polymerase II proximal promoter sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FOXJ1

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FOXJ1

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

occurs_at:(SO:0001952)

Seeded From UniProt

complete

MOUSE:FOXJ1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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