Zfp217, also known as ZNF217 in humans, is a member of the krüppel-type zinc finger protein family. It plays diverse roles in cell differentiation, development, and is involved in multiple biological processes such as adipogenesis, pluripotency regulation, and tumorigenesis [3,4]. It couples gene transcription to m6A mRNA modification, a key epigenetic modification of mRNA, which impacts gene expression and various cellular functions [1].

In adipogenesis, Zfp217 promotes this process. Depletion of Zfp217 in 3T3L1 cells compromises adipogenic differentiation. It modulates m6A mRNA methylation by activating FTO transcription, and its interaction with YTHDF2 is crucial for FTO-m6A interaction. Loss of Zfp217 leads to FTO decrease and augmented m6A levels [1]. In another study, Zfp217 knockdown in cells prevented mitotic clonal expansion, inhibited adipogenesis, and affected m6A-related regulation of cyclin D1 mRNA [2]. In mice, global Zfp217 heterozygous knockout (Zfp217+/-) resisted high-fat diet-induced obesity, with improved metabolic profiles, reduced adipogenesis in inguinal white adipose tissue, and decreased adipogenesis in mouse embryonic fibroblasts [5]. In uterine leiomyosarcoma, Zfp217 functions at early tumor-initiation stages, and its human homolog ZNF217 is elevated in human tumors, negatively correlating with patient prognosis [6].

In summary, Zfp217 is a significant regulator in adipogenesis and energy metabolism, and its dysregulation is associated with obesity-related disorders. In cancer, especially uterine leiomyosarcoma, Zfp217 may act as an oncogene. Studies using Zfp217 knockout mouse models have provided crucial insights into its functions in these biological processes and disease conditions, highlighting its potential as a therapeutic target.