DIO2 gene expression is stimulated by EBF2 and repressed by ZNF423

Stable Identifier
R-HSA-9844598
Type
Reaction [omitted]
Species
Homo sapiens
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ReviewStatus
5/5
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DIO2 gene encodes type II iodothyronine deiodinase, which is essential for adaptive thermogenesis in brown adipose tissue, as one of the regulators of the adaptive thermogenesis is the thyroid hormone T3 (3,5,3’-triiodothyronine). Based entirely on different mouse studies cited below DIO2 gene is annotated as a candidate EBF2 target gene, as direct binding of EBF2 to the regulatory regions of this gene has not been reported. EBF2 promotes DIO2 gene expression in white adipocytes during their transition to beige adipocytes (Rajakumari et al. 2013), while knockdown of EBF2 mRNA in beige adipocytes leads to downregulation of DIO2 (Pearson et al. 2019). Upregulation of Blnc1, a lncRNA that interacts with the transcription factor EBF2 and stimulates EBF2-mediated induction of gene involved in beige and brown adipogenesis, is associated with upregulation of DIO2 mRNA expression (Zhao et al. 2014; Mi et al. 2017). Depletion of DPF3, a subunit of the BAF chromatin remodeling complex that binds EBF2 and promotes transcription of EBF2 target genes, leads to downregulation of DIO2 mRNA (Shapira et al. 2017). Ectopic overexpression of ID1, which was reported to bind to and negatively regulate EBF2, leads to reduced DIO2 expression (Patil et al. 2017). ZNF423, an inhibitor of EBF2 transcriptional activity, represses DIO2 gene expression (Shao et al. 2016; Shao et al. 2021) and the repression is dependent on the ability of ZNF423 to interact with the NuRD transcriptional repressor complex (Shao et al. 2021).
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