SERUM RESPONSE ELEMENT-LIKE SEQUENCES OF THE HUMAN LOW-DENSITY-LIPOPROTEIN RECEPTOR PROMOTER - POSSIBLE REGULATION SITES FOR STEROL-INDEPENDENT TRANSCRIPTIONAL ACTIVATION

Serum factors stimulate low density lipoprotein receptor (LDLR) gene e xpression in HepG2 cells through sterol-independent pathways. Promoter element other than sterol regulatory element-1 (SRE-1) seems to be ne cessary. Protein binding activity of the human LDLR promoter fragment (550bp) beyond the SRE-1 was determined by DNase I footprint assay. Fi ve different promoter regions were protected from DNase I digestion; - 226 to -258, -291 to -304, -324 to -336, -360 to -373, and -521 to -52 8. The regions of -324 to -336 and -521 to -528 showed serum response element (SRE)-like consensus sequence of CC(A/T)(6)GG. Serum incubatio n affected the protection degree of the SRE-like elements, but 25-hydr oxycholesterol did not. It is proposed, therefore, that the promoter r egion of -324 to -336 and/or -521 to -528 in human LDLR gene may be re sponsible for the rapid activation of the gene transcription by serum factor in a sterol-independent manner.