Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs

Nicolas Dif , Vanessa Euthine , Estelle Gonnet , Martine Laville , Hubert Vidal , Etienne Lefai (1)

1 MMD - Mécanisme Moléculaire du Diabète

In the present work, we aimed to decipher the mechanisms involved in the transcriptional effect of insulin on the SREBP-1c specific promoter of the human srebf-1 gene. Using luciferase reporter gene constructs in HEK 293 cells, we demonstrated that the full effect of insulin requires the presence of sterol response elements (SRE) in the proximal region of the promoter. Furthermore, insulin increases the binding of SREBP-1 to this promoter region in ChIP assay. We also found that the nuclear receptor LXRs strongly activate SREBP-1c gene expression and identified the LXR response element involved in this effect. However, our data suggested that these LXREs do not play a major role in the response to insulin. Finally, using expression vectors and adenoviruses allowing ectopic overexpressions of the human mature forms of SREBP-1a or SREBP-1c we demonstrated the direct role of SREBP-1 in the control of SREBP-1c gene expression in human skeletal muscle cells. Altogether, these data strongly suggest that the transcription factors SREBP-1 are the main mediators of insulin action on SREBP-1c expression in human tissues.

Mots clés: Life Sciences

Nicolas Dif, Vanessa Euthine, Estelle Gonnet, Martine Laville, Hubert Vidal, et al.. Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs. Biochemical Journal, 2006, 400 (1), pp.179-188. ⟨10.1042/BJ20060499⟩. ⟨hal-00478570⟩