ZFP217 regulates adipogenesis by controlling mitotic clonal expansion in a METTL3-m6A dependent manner
- PMID: 31434544
- PMCID: PMC7567449
- DOI: 10.1080/15476286.2019.1658508
ZFP217 regulates adipogenesis by controlling mitotic clonal expansion in a METTL3-m6A dependent manner
Abstract
Obesity is becoming a global problem. Research into the detailed mechanism of adipocyte development is crucial for the treatment of excess fat. Zinc finger protein 217 plays roles in adipogenesis. However, the underlying mechanism remains unclear. Here, we demonstrated that ZFP217 knockdown prevented the mitotic clonal expansion process and caused adipogenesis inhibition. Depletion of ZFP217 increased the expression of the m6A methyltransferase METTL3, which upregulated the m6A level of cyclin D1 mRNA. METTL3 knockdown rescued the siZFP217-inhibited MCE and promoted CCND1 expression. YTH domain family 2 recognized and degraded the methylated CCND1 mRNA, leading to the downregulation of CCND1. Consequently, cell-cycle progression was blocked, and adipogenesis was inhibited. YTHDF2 knockdown relieved siZFP217-inhibited adipocyte differentiation. These findings reveal that ZFP217 knockdown-induced adipogenesis inhibition was caused by CCND1, which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner. We have provided novel insight into the underlying molecular mechanisms by which m6A methylation is involved in the ZFP217 regulation of adipogenesis.
Keywords: METTL3; ZFP217; adipogenesis; mRNA m6A; mitotic clonal expansion.
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References
-
- Lee SW, Son JY, Kim JM, et al. Body fat distribution is more predictive of all-cause mortality than overall adiposity. Diabetes Obesity Metab. 2018;20:141–147. - PubMed
-
- Buzaglo-Azriel L, Kuperman Y, Tsoory M, et al. Loss of muscle MTCH2 increases whole-body energy utilization and protects from diet-induced obesity. Cell Rep. 2017;18:1335–1336. - PubMed
-
- Esteve RM. Adipose tissue: cell heterogeneity and functional diversity. Endocrinol Nutr. 2014;61:100–112. - PubMed
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