Hb. Sanchez et al., COOPERATION BY STEROL REGULATORY ELEMENT-BINDING PROTEIN AND SP1 IN STEROL REGULATION OF LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE, The Journal of biological chemistry, 270(3), 1995, pp. 1161-1169
Regulation of the low density lipoprotein (LDL) receptor promoter by c
holesterol requires a well defined sterol regulatory site and an adjac
ent binding site for the universal transcription factor Sp1. These ele
ments are located in repeats 2 and 3 of the wild type promoter, respec
tively, The experiments reported here demon strate that Sp1 participat
es in sterol regulation of the LDL receptor in an orientation-specific
fashion. We pre sent data which suggest that sterol regulatory elemen
t binding protein (SREBP) increases the binding of Sp1 to the adjacent
repeat 3 sequence. We also demonstrate that SREBP and Sp1 synergistic
ally activate expression from the LDL receptor promoter inside the cel
l by cotransfecting expression vectors encoding each protein into Dros
ophila tissue culture cells that are devoid of endogenous Sp1. In addi
tion, other transcription factor sites were unable to substitute for S
p1 in sterol regulation when placed next to the SREBP-binding site, Th
ese studies together with recent data from others provide the basis of
a working model for sterol regulation of the LDL receptor promoter, T
he presence of Sp1 sites in several other regulated promoters suggests
that this universal transcription factor has been recruited to partic
ipate in many regulatory responses possibly by a similar mechanism.