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PMID:16467207

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Citation

Dame, C, Kirschner, KM, Bartz, KV, Wallach, T, Hussels, CS and Scholz, H (2006) Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin gene. Blood 107:4282-90

Abstract

Molecular mechanisms for the developmental stage and tissue-specific regulation of the erythropoietin (EPO) gene are poorly understood. Recent findings indicate a role of the Wilms tumor suppressor, Wt1, in the formation of the hematopoietic system. Herein, we tested the hypothesis that Wt1 is a transcriptional regulator of the EPO gene. Binding of the transcriptionally competent Wt1(-KTS) isoform to the minimal EPO promoter was demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation. Under normoxia, EPO expression was significantly increased in HEK 293 and HepG2 cells with forced expression of Wt1(-KTS). A reporter construct harboring the 117-bp minimal human EPO promoter was activated up to 20-fold by transient cotransfection of Wt1(-KTS) in different cell lines. Mutation of the Wt1 binding site in the EPO promoter abrogated this stimulatory effect of the Wt1(-KTS) protein. Hepatic Epo mRNA expression was significantly reduced in embryonic mice with homozygous Wt1 deletion. Furthermore, Wt1 and EPO were colocalized in hepatocytes of the liver and in neuronal cells of the dorsal root ganglia in developing mice. Both proteins were also detected in Sertoli cells of the adult murine testis. In conclusion, we identified Wt1(-KTS) as a novel transcriptional activator for the tissue-specific expression of the EPO gene.

Links

PubMed Online version:10.1182/blood-2005-07-2889

Keywords

Animals; Binding Sites; Cell Line, Tumor; Embryo, Mammalian/cytology; Embryo, Mammalian/metabolism; Erythropoietin/genetics; Humans; Mice; Mutation; Promoter Regions, Genetic; RNA, Messenger/analysis; Tissue Distribution; Transcription Factors/physiology; Transfection; WT1 Proteins/physiology

Significance

Annotations

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

HUMAN:WT1

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:WT1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:WT1

enables

GO:0044212: transcription regulatory region DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:WT1

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WT1

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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