PMID- 11829738 OWN - NLM STAT- MEDLINE DCOM- 20020322 LR - 20190501 IS - 0264-6021 (Print) IS - 1470-8728 (Electronic) IS - 0264-6021 (Linking) VI - 362 IP - Pt 1 DP - 2002 Feb 15 TI - Structural and functional characterization of the human and mouse fibulin-1 gene promoters: role of Sp1 and Sp3. PG - 41-50 AB - Fibulin-1 is a multifunctional extracellular protein involved in diverse biological processes including cardiovascular development, haemostasis and cancer. To investigate the transcriptional regulation of the gene encoding fibulin-1 we cloned and analysed about 4.0 kb of the 5'-flanking regions of both the human and mouse fibulin-1 genes. The human and mouse fibulin-1 promoters share little sequence similarity except for a short region of approx. 150-170 bp immediately upstream of the translation start site. The conserved region contains a TATA-like sequence (ATAATT) and multiple consensus binding sites for Sp1 and activator protein 2 (AP-2). That the short conserved region in each gene confers basal promoter activity is demonstrated by transient transfections of promoter deletion constructs for both the human and mouse genes into cells that express fibulin-1 constitutively. Co-transfections of promoter constructs with expression plasmids for Sp1, Sp3 and Sp4 into Drosophila SL2 cells indicate that Sp1 and Sp3 are essential for transcriptional activation and that these two factors act synergistically. Electrophoretic mobility-shift assays show that Sp1 and Sp3, but not AP-2, bind to the basal promoter of the human fibulin-1 gene. The results demonstrate the functional importance of Sp1 and Sp3 in regulating the expression of the fibulin-1 gene. FAU - Castoldi, Mirco AU - Castoldi M AD - Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, U.S.A. FAU - Chu, Mon-Li AU - Chu ML LA - eng SI - GENBANK/AY040588 SI - GENBANK/AY040589 GR - GM 55625/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (Calcium-Binding Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (SP3 protein, human) RN - 0 (Sp1 Transcription Factor) RN - 0 (Sp3 protein, mouse) RN - 0 (Transcription Factors) RN - 0 (fibulin) RN - 148710-94-5 (Sp3 Transcription Factor) SB - IM MH - Animals MH - Base Sequence MH - Calcium-Binding Proteins/*genetics MH - Cells, Cultured MH - Cloning, Molecular MH - DNA-Binding Proteins/*physiology MH - Humans MH - Mice MH - Molecular Sequence Data MH - *Promoter Regions, Genetic MH - Sequence Homology, Nucleic Acid MH - Sp1 Transcription Factor/*physiology MH - Sp3 Transcription Factor MH - Transcription Factors/*physiology MH - Transcription, Genetic PMC - PMC1222358 EDAT- 2002/02/07 10:00 MHDA- 2002/03/23 10:01 PMCR- 2002/08/15 CRDT- 2002/02/07 10:00 PHST- 2002/02/07 10:00 [pubmed] PHST- 2002/03/23 10:01 [medline] PHST- 2002/02/07 10:00 [entrez] PHST- 2002/08/15 00:00 [pmc-release] AID - 10.1042/0264-6021:3620041 [doi] PST - ppublish SO - Biochem J. 2002 Feb 15;362(Pt 1):41-50. doi: 10.1042/0264-6021:3620041.