Regulation of the bovine SCD5 promoter by EGR2 and SREBP1.

In rodents, the transcription factors early growth response 2 (EGR2) and sterol regulatory element binding protein 1a (SREBP1a) regulate transcription of the stearoyl-CoA desaturase 2 (SCD2) gene during peripheral nerve myelination, which may be important for synthesis of the lipid component of myelin. Most non-rodent genomes do not contain the SCD2 gene, but rather express SCD5 in brain and nervous tissues. In this paper, we asked whether bovine SCD5 is regulated in a similar manner to rodent SCD2. Expression of EGR2 did not result in an increase in endogenous SCD5 mRNA expression in JEG3 cells, but did result in activation of truncated bovine SCD5 promoter luciferase reporter constructs. Similar results were obtained with expression of the active form of SREBP1a; however, unlike rodent SCD2, there was no synergistic activation of the bovine SCD5 promoter reporters when EGR2 and SREBP1a were co-expressed. Mutation of the putative EGR2 binding site in the SCD5 promoter abolished activation by SREBP1a, suggesting that EGR2 and SREBP1a bind to the same site in the SCD5 promoter. Finally, we have identified a region of the bovine SCD5 promoter between 505 and 305 base pairs upstream of the transcriptional start site that appears to be important for maintaining basal levels of transcription of this gene. While it appears that there are some differences between the regulation of rodent SCD2 and bovine SCD5, the promoters of both genes can be activated by EGR2 and SREBP1a. This is the first report of potential regulators of SCD5 transcription.