Jn. Athanikar et al., PROMOTER SELECTIVE TRANSCRIPTIONAL SYNERGY MEDIATED BY STEROL REGULATORY ELEMENT-BINDING PROTEIN AND SP1 - A CRITICAL ROLE FOR THE BTD DOMAIN OF SP1, Molecular and cellular biology, 17(9), 1997, pp. 5193-5200
Cellular cholesterol and fatty acid levels : are coordinately regulate
d by a family of transcriptional regulatory proteins designated sterol
regulatory element binding proteins (SREBPs). SREBP-dependent transcr
iptional activation from all promoters examined thus far is dependent
on the presence of an additional binding site for a ubiquitous coactiv
ator, In the low-density lipoprotein (LDL) receptor, acetyl coenzyme A
carboxylase (ACC), and fatty acid synthase (FAS) promoters, which are
all regulated by SREBP, the coactivator is the transcription factor S
pl, In this report, we demonstrate that Sp3, another member of the Spl
family, is capable of substituting for Spl in coactivating transcript
ion from all three of these promoters, Results of an earlier study sho
wed that efficient activation of transcription from the LDL receptor p
romoter required domain C of Spl; however, this domain is not crucial
for activation of the simian virus 40 promoter, where synergistic acti
vation occurs through multiple Spl binding sites and does not require
SREBP, Also in the present report, we further localize the critical de
terminant of the C domain required for activation of the LDL receptor
to a small region that is highly conserved between Spl and Sp3. This c
rucial domain encompasses the buttonhead box, which is a 10-amino-acid
stretch that is present in several Spl family members, including the
Drosophila buttonhead gene product, Interestingly, neither the buttonh
ead box nor the entire C domain is required for the activation of the
FAS and ACC promoters even though both SREBP and Spl are critical play
ers. ACC and FAS each contain two critical SREBP sites, whereas there
is only one in the LDL receptor promoter, This finding suggested that
buttonhead-dependent activation by SREBP and Spl may be limited to pro
moters that naturally contain a single SREBP recognition site, Consist
ent with this model, a synthetic construct containing three tandem cop
ies of the native LDL receptor SREBP site linked to a single Spl site
was also significantly activated in a buttonhead-independent fashion.
Taken together, these studies indicate that transcriptional activation
through the concerted action of SREBP and Spl can occur by at least t
wo different mechanisms, and promoters that are activated by each one
can potentially be identified by the number of critical SREBP binding
sites that they contain.