Eliminating SF-1 (Nr5a1) Sumoylation In Vivo Results in Ectopic Hedgehog Signaling and Disruption of Endocrine Development.
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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-1K119R,K194R or 2KR) and found that Sf-12KR/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. In an immortalized embryonic cell line, the highly SUMO-sensitive target gene Shh is ectopically activated by direct recruitment of unsumoylatable SF-1 to non-canonical DNA binding sites. We propose that sumoylation 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 multi-cellular organisms. Adult and embryonic gene expression in adrenals and testes from SF-1 wild type and 2KR homozygous mice are compared using MEEBO microarrays.
ORGANISM(S): Mus musculus
SUBMITTER: Holly Ingraham
PROVIDER: E-GEOD-30078 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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