Conclusions
PRDM16 is a key transcriptional regulator in beige adipocyte formation and can stimulate nearly all key characteristics of authentic brown fat cells 26. In addition, althoughPRDM16 is introduced before cell differentiation, nearly all adipocytes can be activated to express BAT-selective genes [17]. In this study, we found that BAT-selective genes were up-regulated in PRDM16-overexpressing 3T3-L1 cells compared with the control group, indicating that the mutation inPRDM16 influences the function of this gene in the brown adipogenesis program. PRDM16 regulates thermogenic genes by forming a complex with various transcription factors, includingC/EBPβ ,PGC-1α , PPARα and PPARγ . Although the same differentiation efficiency was induced, the suppression of C/EBPβand PGC-1α mRNA expression levels in the PRDM16 MU group indicated a decreased formation of the transcription complex and finally, the suppression of the expression of thermogenic genes, such asUCP1 , compared with the PRDM16 group. Functional differences in PRDM16 caused by sequence variations could explain why northern cattle are more cold-tolerant than southern cattle. For example, mortality forB. indicus is suggested to be higher than that for B. taurus in the cold [47], which may be a result of exhausting their post-natal BAT lipids [48]. Therefore, on one hand, PRDM16 functioned well in northern cattle is required to resist extreme cold, and on the another hand, the functional inactivation of PRDM16 impairs beige adipocyte formation, which is also beneficial for the environment adaptability of southern cattle. In summary, we compared the whole genomes of northern cattle living in extremely cold environments with those of southern cattle living in warm environments to reveal a new mechanism behind northern cattle’s adaptability to cold environments. This study is the first to propose a molecular mechanism for cattle’s cold-tolerance ability. In particular, we proved that PRDM16 is a forceful genome effector that facilitates the formation of diverse cold-adaptations using functional experiments. These results could improve the comprehension of adaptive genetic variations in cattle living in different temperatures and other livestock species.