Overexpression of DNMT3A promotes proliferation and inhibits differentiation of porcine intramuscular preadipocytes by methylating p21 and PPARg promoters.

Intramuscular fat (IMF), which is modulated by the number and size of intramuscular preadipocytes, plays a key role in pork quality. DNA (cytosine-5)-methyltransferase 3A (DNMT3A), an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, is involved in the management of diverse intracellular processes. However, the physiological functions of DNMT3A in proliferation and differentiation of porcine intramuscular preadipocytes have not been clearly established. Here, we found that DNMT3A significantly promoted the proliferation, while inhibited the differentiation of intramuscular preadipocytes. We demonstrated that overexpression of DNMT3A promoted the expression of cell proliferation markers but significantly decreased the expression of p21 to repress cell proliferation by the methylation of p21 promoter. Moreover, overexpression of DNMT3A decreased lipid accumulation and significantly down-regulated the levels of adipogenic marker genes including PPARg (Peroxisome proliferator-activated receptor gamma), SREBP-1c (Sterol regulatory element-binding protein 1c), and aP2 (FABP4, fatty acid binding protein 4) through the methylation of PPARg promoter. The blocking effect of DNMT3A on adipogenesis can be rescued by rosiglitazone treatment. Collectively, these findings illustrated the essential role of DNMT3A in the proliferation and differentiation of porcine intramuscular preadipocytes, and provide a potential target to improve pork quality.