SP3 and AP-1 mediate transcriptional activation of the lamin A proximal promoter

Lamin A is a major component of the nuclear lamina that is expressed in var ious types of differentiated cells. We have analysed previously the putativ e promoter sequences of the gene and shown that the rat lamin A proximal pr omoter contains two essential motifs, a GC box that can bind to Sp1 and Sp3 , and an AP-1 motif that can bind to c-Jun and c-Fos. In this study we have investigated the role of Sp1 and Sp3 in transactivation of the promoter. F unctional analysis of the promoter in Drosophila SL2 cells has demonstrated that it is inactive in the absence of Sp proteins. Activation by expressio n of Sp3 is more pronounced than that by Sp1 although both proteins can bin d to the GC box in vitro; activation clearly depends on an intact GC box as deduced from mutant analysis. Promoter activity in SL2 cells also requires an intact AP-I motif, which can bind to endogenous Drosophila Jun and Fos proteins. Furthermore, overexpression of c-Jun and c-Fos results in fourfol d activation of the promoter in PCC-4 embryonal carcinoma cells. Our demons tration that activation of the lamin A proximal promoter is mediated by Sp3 and AP-1 transcription factors affords a basis for further studies on the regulation of this important gene during development and disease.