Yin Yang 1 Is Essential for Transcriptional Activation of the Bovine Sirt2 Gene in Preadipocytes.

Abstract

Sirtuin 2 (Sirt2) belongs to the NAD+-dependent deacetylase family, is more highly expressed than other family members in adipocytes, and plays crucial roles in a wide range of biological processes. However, the mechanisms underlying Sirt2 expression during adipogenesis are poorly studied. In this study, the transcriptional start site (TSS) of Sirt2 was identified and two alternative transcript variants were spliced from Sirt2. The 5'-regulatory region of Sirt2 was also characterized; no TATA-box or CCAAT-box was presented in the 5'-flanking region. Two cytosine-phosphate diester-guanine (CpG) islands were also identified between nucleotides -563 and +4. A dual-luciferase reporter assay revealed that a 178 base pair sequence upstream from the TSS (+1) was the core promoter of Sirt2. Results from a site-directed mutagenesis experiment, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay indicated Yin Yang 1 (YY1) to be a positive regulator of bovine Sirt2 in preadipocytes. YY1 is likely to suppress adipogenesis in two different ways by regulating peroxisome proliferator-activated receptor gamma expression. Our results expand the information on the regulatory network of adipogenesis, which is an important basis for improving beef quality, treating obesity, and other related diseases.