TET2 is recruited by CREB to promote , , and transcription by facilitating hydroxymethylation during adipocyte differentiation.

Ten-eleven translocation proteins (TETs) are dioxygenases that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an important epigenetic mark that regulates gene expression during development and differentiation. Here, we found that the TET2 expression was positively associated with adipogenesis. Further, and experiments showed that TET2 deficiency blocked adipogenesis by inhibiting the expression of the key transcription factors CCAAT/enhancer-binding protein beta (C/EBPβ), C/EBPα and peroxisome proliferator-activated receptor gamma (PPARγ). In addition, TET2 promoted 5hmC on the CpG islands (CGIs) of , and at the initial time point of their transcription, which requires the cAMP-responsive element-binding protein (CREB). At last, specific knockout of in preadipocytes enabled mice to resist obesity and attenuated the obesity-associated insulin resistance. Together, TET2 is recruited by CREB to promote the expression of , and via 5hmC during adipogenesis and may be a potential therapeutic target for obesity and insulin resistance.