Localization of a Negative Thyroid Hormone-response Region in Hepatic Stearoyl-CoA Desaturase Gene 1

The effect of thyroid hormone on stearoyl-CoA desaturase gene 1 (SCD1) expression was investigated in mouse liver. Daily injections of 15 micrograms triiodothyronine (T3)/100 g body weight to hypothyroid mice resulted in repression of SCD1 mRNA levels by more than 50% in 48 hours and up to 65% in 6 days. Transient co-transfections were performed with an expression vector for T3 receptor alpha (T3R alpha) in HepG2 cells using chimeric reporter gene constructs of the SCD1 5'-flanking region. Transcriptional repression of the SCD1 putative promoter was observed upon treatment with 100 nM T3 when cotransfected with T3R alpha, but not without cotransfection of receptor. Transient gene expression studies localized a T3 response region to a 70-bp sequence in the SCD1 putative promoter. Eliminating the TATA box and an AP-2 binding site, DNA mobility shift analysis demonstrated specific binding of in vivo nuclear protein from mouse liver nuclear extract to a 43-bp sequence. DNA mobility shift with purified T3R alpha confirmed the presence of a T3 receptor binding site in this thyroid hormone-responsive region. These data indicate that SCD1 contains a negative T3 response region in its proximal promoter.