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.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adrenal Glands / embryology
-
Adrenal Glands / growth & development
-
Animals
-
Animals, Newborn
-
Antigens, CD
-
Antigens, Differentiation, B-Lymphocyte
-
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
-
Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
-
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
-
Zinc Finger Protein GLI1
Substances
-
Antigens, CD
-
Antigens, Differentiation, B-Lymphocyte
-
Carrier Proteins
-
Gli1 protein, mouse
-
Hedgehog Proteins
-
Kruppel-Like Transcription Factors
-
Membrane Proteins
-
Platelet Endothelial Cell Adhesion Molecule-1
-
SOX9 Transcription Factor
-
Siglece protein, mouse
-
Sox9 protein, mouse
-
Steroidogenic Factor 1
-
Zinc Finger Protein GLI1
-
steroidogenic factor 1, mouse
-
Testosterone
-
Corticosterone