TATA Element Modulatory Factor 1 Negatively Regulates Sodium Acetate Activated Milk Fat Synthesis Through SREBP1 Pathway in Bovine Mammary Epithelial Cells

Abstract

Background: Sodium acetate is one of the important nutrients that regulate milk fat synthesis in bovine mammary epithelial cells (BMECs), and it regulates milk fat synthesis mainly through the SREBP1 pathway. Our previous study has showed that TATA element modulatory factor 1 (TMF1) may be interacts with SREBP1 and regulates the sodium acetate-dependent milk synthesis in BMECs, but the underlying mechanism is unclear. In the current study, the effect of TMF1 on sodium acetate activated milk fat synthesis in BMECs was assessed. Results: Overexpressing or inhibiting TMF1 demonstrated that TMF1 negatively regulated sodium acetate activated sterol regulatory element-binding protein 1 (SREBP1) pathway and milk fat synthesis; Overexpressing or inhibiting SREBP1 showed that TMF1 inhibited sodium acetate activated milk fat synthesis through SREBP1 pathway; Co-immunoprecipitation analysis showed that TMF1 interacted with SREBP1; Nuclear localization of SREBP1 analysis showed that sodium acetate activated nuclear localization of SREBP1 was inhibited by TMF1; Depletion or supply sodium acetate demonstrated that sodium acetate negatively regulated expression of TMF1 and the interaction between TMF1 and SREBP1. Conclusions: Together, these results indicate that TMF1 is a negative regulatory factor for sodium acetate activated milk fat synthesis, it induced expression by sodium acetate depletion, and interacts with SREBP1 in cytoplasmic, prevents the nuclear localization of SREBP1 and then suppresses the expression of SREBP1 target gene and subsequent milk fat synthesis in BMECs.