INSULIN-LIKE GROWTH-FACTOR-I REGULATES TRANSCRIPTION OF THE ELASTIN GENE THROUGH A PUTATIVE RETINOBLASTOMA CONTROL ELEMENT - A ROLE FOR SP3ACTING AS A REPRESSOR OF ELASTIN GENE-TRANSCRIPTION
Kj. Conn et al., INSULIN-LIKE GROWTH-FACTOR-I REGULATES TRANSCRIPTION OF THE ELASTIN GENE THROUGH A PUTATIVE RETINOBLASTOMA CONTROL ELEMENT - A ROLE FOR SP3ACTING AS A REPRESSOR OF ELASTIN GENE-TRANSCRIPTION, The Journal of biological chemistry, 271(46), 1996, pp. 28853-28860
Previous studies have demonstrated that insulin-like growth factor-I (
IGF-I) increases elastin gene transcription in aortic smooth muscle ce
lls and that this up-regulation is accompanied by a loss of protein bi
nding to the proximal promoter. Sp1 has been identified as one of the
factors whose binding is lost, and in the present study we show that S
p3 binding is also abrogated by IGF-I, but in a selected manner. In fu
nctional analyses using Drosophila SL-2 cells, Sp1 expression can driv
e transcription from the elastin proximal promoter, while co expressio
n of Sp3 results in a repression of Sp1 activity. Footprint and gel sh
ift analyses position the IGF-I responsive sequences to a putative ret
inoblastoma control element (RCE). Mutation of the putative RCE sequen
ce as assessed by transient transfection of smooth muscle cells result
s in an increase in reporter activity equal in magnitude to that confe
rred by IGF-I on the wild type promoter. Together these results suppor
t the hypothesis that IGF-I-mediated increase in elastin transcription
occurs via a mechanism of derepression involving the abrogation of a
repressor that appears to be Sp3 binding to the RCE.