Expression of the human PDGF-B gene is regulated by both positively and negatively acting cell type-specific regulatory elements located in the first intron.
AUTOR(ES)
Franklin, G C
RESUMO
Potential cis-acting regulatory elements of the human platelet derived growth factor-B (PDGF-B) gene were identified by DNase I hypersensitive site mapping. The transcription unit was examined for the presence of hypersensitive sites in chromatin DNA isolated from human term placental cytotrophoblasts, human placental fibroblasts, the JEG-3 choriocarcinoma cell line and the U2-OS osteosarcoma cell line. A number of cell type-specific hypersensitive sites were identified, all within the 1st intron. Transient transfection of JEG-3 cells with CAT constructs containing regions of the c-sis 1st intron linked to the basal c-sis promoter identified a cell type-specific positive regulatory activity within the intron, composed of at least two distinct elements. One element appeared to be specific for JEG-3 cells, while the other was also active in U2-OS cells. The overall positive regulatory activity of the 1st intron region was specific for JEG-3 cells, but did not function as a classically defined enhancer, as it was orientation-dependent (unless stably integrated into chromatin DNA). In addition, the activator appears to require interaction with the c-sis promoter, as little or no activation was seen when either the SV40 or human beta-globin promoters were substituted for the c-sis promoter. The 1st intron also contained a negative regulatory element, which was specific for U2-OS cells and silenced an abnormally high basal c-sis promoter activity in these cells. The complexity of the transcriptional control of the PDGF-B gene is discussed.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=452796Documentos Relacionados
- An S1 nuclease-sensitive region in the first intron of human platelet-derived growth factor A-chain gene contains a negatively acting cell type-specific regulatory element.
- Triplex targeting of human PDGF-B (c-sis, proto-oncogene) promoter specifically inhibits factors binding and PDGF-B transcription
- Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall
- Cell type-specific transcriptional regulation of the human adenosine deaminase gene.
- Systemic and cell type-specific gene expression patterns in scleroderma skin