Zfp217, also known as zinc finger protein 217, is a member of the krüppel-type zinc finger protein family. It plays diverse roles in cell differentiation, development, and is involved in regulating gene expression programs. It has been linked to processes such as adipogenesis, pluripotency, and cancer-related chemoresistance, highlighting its overall biological importance. Genetic models, especially KO mouse models, have been crucial in understanding its functions [3,5].

In adipogenesis, Zfp217 knockdown in 3T3L1 cells and mouse embryonic fibroblasts compromises adipogenic differentiation. In 3T3L1 cells, depletion of Zfp217 leads to a global increase of m6A modification by affecting the transcription of m6A demethylase FTO and the interaction with YTHDF2 [1]. In another study, Zfp217 knockdown in mice prevents mitotic clonal expansion, inhibits adipogenesis, and is mediated by METTL3-m6A-YTHDF2 pathway on cyclin D1 mRNA [2]. Global Zfp217 heterozygous knockout (Zfp217+/-) mice resist high-fat diet-induced obesity, showing improved metabolic profiles and reduced adipogenesis-related genes in inguinal white adipose tissue [4].

In conclusion, Zfp217 is a key regulator in adipogenesis and energy metabolism. The gene knockout mouse models have provided valuable insights into the role of Zfp217 in obesity-related conditions, suggesting it could be a potential target for obesity treatment strategies. Its functions in coordinating transcriptional and post-transcriptional regulation through m6A mRNA methylation further emphasize its importance in biological processes [1,2,4].

References:

1. Song, Tongxing, Yang, Yang, Wei, Hongkui, Jiang, Siwen, Peng, Jian. . Zfp217 mediates m6A mRNA methylation to orchestrate transcriptional and post-transcriptional regulation to promote adipogenic differentiation. In Nucleic acids research, 47, 6130-6144. doi:10.1093/nar/gkz312. https://pubmed.ncbi.nlm.nih.gov/31037292/

2. Liu, Qing, Zhao, Yuanling, Wu, Ruifan, Wang, Yizhen, Wang, Xinxia. 2019. ZFP217 regulates adipogenesis by controlling mitotic clonal expansion in a METTL3-m6A dependent manner. In RNA biology, 16, 1785-1793. doi:10.1080/15476286.2019.1658508. https://pubmed.ncbi.nlm.nih.gov/31434544/

3. Lee, Dung-Fang, Walsh, Martin J, Aguiló, Francesca. 2016. ZNF217/ZFP217 Meets Chromatin and RNA. In Trends in biochemical sciences, 41, 986-988. doi:10.1016/j.tibs.2016.07.013. https://pubmed.ncbi.nlm.nih.gov/27519282/

4. Zeng, Qianhui, Wang, Nannan, Zhang, Yaru, Qiao, Tong, Jiang, Siwen. 2021. Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice. In International journal of molecular sciences, 22, . doi:10.3390/ijms22105390. https://pubmed.ncbi.nlm.nih.gov/34065474/

5. Xiang, Hong, Zhong, Zhu-Xia, Peng, Yong-Dong, Jiang, Si-Wen. 2017. The Emerging Role of Zfp217 in Adipogenesis. In International journal of molecular sciences, 18, . doi:10.3390/ijms18071367. https://pubmed.ncbi.nlm.nih.gov/28653987/