Znf423 binds Ebf2 at Ebf2-target gene loci

Stable Identifier
R-MMU-9844373
Type
Reaction [transition]
Species
Mus musculus
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ReviewStatus
5/5
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Znf423 binds Ebf2 at Ebf2-target gene loci
In mouse adipocytes, the transcription factor Znf423 (also known as Zfp423), whose expression is enriched in white compared with brown adipocytes, can from a complex with Ebf2 at Ebf2 target gene loci and suppress activation of Ebf2 target genes that are part of the thermogenic program in brown and beige adipocytes (Shao et al. 2016; Shao et al. 2021). The transcriptional repression of Ebf2 target genes by Znf423 involves Znf423-mediated recruitment of the transcriptional repressor complex NuRD (composed of, at least, core components Mta1 or Mta2 or Mta3, Mbd3, the dimer of Hdac1 and Hdac2, Rbbp4 and Rbbp7, and peripherally associated proteins Chd3 or Chd4 and Gatad2a or Gatad2b) and interference with the recruitment of the transcription factor Pparg to the Ebf2 target gene loci.

The following Ebf2 target genes have been shown to be negatively regulated by Znf423:
Cidea (Shao et al. 2021: inability of ectopically expressed Znf423 mutant defective in NuRD binding to repress Cidea gene transcription in mouse brown adipocytes);
Dio2 (Shao et al. 2016: significant increase in Dio2 mRNA levels upon knockout of Znf423 gene in mouse white adipocytes; Shao et al. 2021: inability of ectopically expressed Znf423 mutant defective in NuRD binding to repress Dio2 gene transcription in mouse brown adipocytes);
Elovl3 (Shao et al. 2016: significant upregulation of Elovl3 gene transcription by Znf423 knockout in mouse white adipocytes);
Ppara (Shao et al. 2021: by ChIP qPCR, Znf423 gene deletion does not interfere with Ebf2 binding but promotes Pparg binding to the Ppara gene locus; Znf423 binds to the Ppara gene regulatory elements);
Prdm16 (Shao et al. 2016: inhibition of induction of Prdm16 gene transcription by ectopically expressed Ebf2 in mouse white adipocytes by co-expression of Znf423; reduced induction of Prdm16 luciferase reporter gene by Ebf2 and the complex of Pparg2:Rxra in the presence of Znf423; Shao et al. 2021: by ChIP qPCR, Znf423 gene deletion does not interfere with Ebf2 binding but promotes Pparg binding to the Prdm16 gene locus);
Ucp1 (Shao et al. 2016: expression of Ucp1 gene at both mRNA and protein levels is significantly increased by Znf423 knockdown or Znf423 gene knockout in mouse white adipocytes, while expression of Ucp1 is repressed by ectopic Znf423 overexpression in brown and beige adipocytes; Shao et al. 2021: by ChIP qPCR, Znf423 gene deletion does not interfere with Ebf2 binding but promotes Pparg binding to the Ucp1 gene locus);

Based on the strength of experimental evidence, Ucp1, Ppara, and Prdm16 genes are annotated as members of Znf423 target gene set, while Cidea, Dio2, and Elovl3 are annotated as candidates of Znf423 target gene set.
Literature References
PubMed ID Title Journal Year
34620682 ZFP423 controls EBF2 coactivator recruitment and PPARγ occupancy to determine the thermogenic plasticity of adipocytes

Shan, B, Shao, M, Seale, P, Vishvanath, L, Zhang, Q, Li, L, Gupta, RK, Truong, A

Genes Dev 2021
27238639 Zfp423 Maintains White Adipocyte Identity through Suppression of the Beige Cell Thermogenic Gene Program

MacPherson, KA, Kusminski, CM, Shao, M, Seale, P, Vishvanath, L, Holland, WL, Sun, K, Hepler, C, Wang, QA, Gupta, RK, Spurgin, SB, Ishibashi, J

Cell Metab 2016
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