In vivo role of the SP1 site neighboring sterol-responsive element-1 in controlling low-density lipoprotein receptor gene expression

The in vivo role of the crucial Sp1 site neighboring sterol-responsive element-1 (SRE-1) in controlling LDL receptor gene expression in the presence or absence of sterols was examined. For this purpose the Xenopus laevis system was utilized as there are two different genes for LDL receptors in frogs which differ in their promoter region in the Sp1-binding sequence of repeat 3 present immediately adjacent to SRE-1. DNase I footprinting of promoters of both receptors showed differences in the affinity of this Sp1 site to purified transcription factor Sp1. Transcript levels of both LDL receptors were measured in livers of frogs on normal and cholesterol-enriched diets. Basal levels and extent of repression of LDL receptor gene on sterol administration were found to be dependent on the nature of the Sp1 site of repeat 3 under in vivo conditions. We conclude that this Sp1 site acts as a constitutive positive transcriptional element that forms a parr of the active transcription complex irrespective of cellular sterol levels. (C) 1996 Academic Press, Inc.