CIDEA gene expression is stimulated by EBF2 and PPARG and repressed by ZNF423 and NuRD

Stable Identifier
R-HSA-9844600
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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CIDEA gene encodes lipid transferase CIDEA (also known as Cell death activator CIDE-A) that promotes lipid droplet formation by mediating lipid droplet fusion. Based entirely on mouse studies cited below CIDEA gene is annotated as a candidate EBF2 target gene, as no direct binding of EBF2 to the regulatory sequences of this gene has been reported. EBF2 stimulates expression of the CIDEA gene, while targeted Ebf2 knockout in mouse brown fat tissue results in severely reduced expression of the Cidea gene (Rajakumari et al. 2013; Wang et al. 2014). EBF2 promotes CIDEA gene expression in beige adipocytes (Stine et al. 2016). Knockdown of Blnc1, a lncRNA that interacts with the transcription factor EBF2 and stimulates EBF2-mediated induction of gene involved in beige and brown adipogenesis, leads to downregulation of CIDEA mRNA in brown preadipocytes, while Blnc1-transduced preadipocytes show upregulation of CIDEA mRNA (Zhao et al. 2014). EBF2 is required for the formation of the activating histone mark H3K27ac on the CIDEA gene and RNA Pol II recruitment (Shapira et al. 2017). MLL4 is required for the formation of the super-enhancer at the CIDEA gene locus (Lai et al. 2017), with ChIP-seq showing that PPARG binding sites in the CIDEA gene co-localize with H3K4me1 and H3K27ac marks of active chromatin (Brunmeir et al. 2016). The transcription factor SIX1, which directly interacts with EBF2, co-localizes with PPARG and activating histone marks at the CIDEA gene enhancer and is able to induce CIDEA gene transcription (Brunmeir et al. 2016). ZNF423, an inhibitor of EBF2 transcriptional activity, represses CIDEA gene expression 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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