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PMID:19050011

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Citation

Green, LM, Wagner, KJ, Campbell, HA, Addison, K and Roberts, SG (2009) Dynamic interaction between WT1 and BASP1 in transcriptional regulation during differentiation. Nucleic Acids Res. 37:431-40

Abstract

The Wilms' tumour suppressor protein WT1 plays a central role in the development of the kidney and also other organs. WT1 can act as a transcription factor with highly context-specific activator and repressor functions. We previously identified Brain Acid Soluble Protein 1 (BASP1) as a transcriptional cosuppressor that can block the transcriptional activation function of WT1. WT1 and BASP1 are co-expressed during nephrogenesis and both proteins ultimately become restricted to the podocyte cells of the adult kidney. Here, we have analysed the WT1/BASP1 complex in a podocyte precursor cell line that can be induced to differentiate. Chromatin immunoprecipitation revealed that WT1 and BASP1 occupy the promoters of the Bak, c-myc and podocalyxin genes in podocyte precursor cells. During differentiation-dependent upregulation of podocalyxin expression BASP1 occupancy of the podocalyxin promoter is reduced compared to that of WT1. In contrast, the repressive WT1/BASP1 occupancy of the c-myc and Bak promoters is maintained and these genes are downregulated during the differentiation process. We provide evidence that the regulation of BASP1 promoter occupancy involves the sumoylation of BASP1. Our results reveal a dynamic cooperation between WT1 and BASP1 in the regulation of gene expression during differentiation.

Links

PubMed PMC2632906 Online version:10.1093/nar/gkn955

Keywords

Animals; Calmodulin-Binding Proteins/analysis; Calmodulin-Binding Proteins/metabolism; Cell Differentiation; Cell Line; Cell Nucleus/chemistry; Cytoskeletal Proteins/analysis; Cytoskeletal Proteins/metabolism; Gene Expression Regulation; Humans; Nerve Tissue Proteins/analysis; Nerve Tissue Proteins/metabolism; Podocytes/cytology; Podocytes/metabolism; Promoter Regions, Genetic; Repressor Proteins/metabolism; Stem Cells/metabolism; Trans-Activators/metabolism; Transcription, Genetic; WT1 Proteins/metabolism

Significance

Annotations

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

MOUSE:WT1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91XV3

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:SUMO3

located_in

GO:0016605: PML body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SUMO3

involved_in

GO:0016925: protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P80723)

Seeded From UniProt

complete

HUMAN:SUMO3

involved_in

GO:1900180: regulation of protein localization to nucleus

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P80723)

Seeded From UniProt

complete

HUMAN:BASP1

located_in

GO:0016605: PML body

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BASP1

located_in

GO:0016363: nuclear matrix

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BASP1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BASP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P22561

F

Seeded From UniProt

complete

MOUSE:BASP1

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BASP1

enables

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

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:BASP1

located_in

GO:0016607: nuclear speck

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BASP1

involved_in

GO:0072112: glomerular visceral epithelial cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:WT1

involved_in

GO:0045892: negative 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

MOUSE:WT1

involved_in

GO:0072112: glomerular visceral epithelial cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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