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PMID:21820362

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Citation

Lee, FY, Faivre, EJ, Suzawa, M, Lontok, E, Ebert, D, Cai, F, Belsham, DD and Ingraham, HA (2011) Eliminating SF-1 (NR5A1) sumoylation in vivo results in ectopic hedgehog signaling and disruption of endocrine development. Dev. Cell 21:315-27

Abstract

Sumoylation is generally considered a repressive mark for many transcription factors. However, the in vivo importance of sumoylation for any given substrate remains unclear and is questionable because the extent of sumoylation appears exceedingly low for most substrates. Here, we permanently eliminated SF-1/NR5A1 sumoylation in mice (Sf-1(K119R, K194R, or 2KR)) and found that Sf-1(2KR/2KR) mice failed to phenocopy a simple gain of SF-1 function or show elevated levels of well-established SF-1 target genes. Instead, mutant mice exhibited marked endocrine abnormalities and changes in cell fate that reflected an inappropriate activation of hedgehog signaling and other potential SUMO-sensitive targets. Furthermore, unsumoylatable SF-1 mutants activated Shh and exhibited preferential recruitment to Shh genomic elements in cells. We conclude that the sumoylation cycle greatly expands the functional capacity of transcription factors such as SF-1 and is leveraged during development to achieve cell-type-specific gene expression in multicellular organisms.

Links

PubMed PMC3157481 Online version:10.1016/j.devcel.2011.06.028

Keywords

Adrenal Glands/embryology; Adrenal Glands/growth & development; Animals; Animals, Newborn; Antigens, CD31/metabolism; Carrier Proteins/metabolism; Cells, Cultured; Corticosterone/metabolism; Electrophoretic Mobility Shift Assay/methods; Embryo, Mammalian; Endocrine System/embryology; Endocrine System/growth & development; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental/genetics; Hedgehog Proteins/genetics; Hedgehog Proteins/metabolism; Immunoprecipitation; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/metabolism; Leydig Cells/metabolism; Leydig Cells/physiology; Male; Membrane Proteins/metabolism; Mice; Mice, Inbred BALB C; Mice, Transgenic; Models, Biological; Mutation/genetics; Oligonucleotide Array Sequence Analysis; SOX9 Transcription Factor/genetics; SOX9 Transcription Factor/metabolism; Signal Transduction/genetics; Signal Transduction/physiology; Spermatozoa/growth & development; Steroidogenic Factor 1/genetics; Steroidogenic Factor 1/metabolism; Sumoylation/genetics; Sumoylation/physiology; Testis/embryology; Testis/growth & development; Testosterone/metabolism; Transfection/methods

Significance

Annotations

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

MOUSE:STF1

acts_upstream_of_or_within

GO:0030325: adrenal gland development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292676

P

Seeded From UniProt

complete

MOUSE:STF1

acts_upstream_of_or_within

GO:0022414: reproductive process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292676

P

Seeded From UniProt

complete

MOUSE:STF1

acts_upstream_of_or_within

GO:0010259: multicellular organism aging

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292676

P

Seeded From UniProt

complete

MOUSE:STF1

acts_upstream_of_or_within

GO:0008584: male gonad development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292676

P

Seeded From UniProt

complete

MOUSE:STF1

acts_upstream_of_or_within

GO:0042445: hormone metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292676

P

Seeded From UniProt

complete


See also

References

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