IN-VIVO FOOTPRINTING AND FUNCTIONAL-ANALYSIS OF THE HUMAN C-SIS PDGF-B GENE PROMOTER PROVIDES EVIDENCE FOR 2 BINDING-SITES FOR TRANSCRIPTIONAL ACTIVATORS

被引:17
作者
DIRKS, RPH [1 ]
JANSEN, HJ [1 ]
VANGERVEN, B [1 ]
ONNEKINK, C [1 ]
BLOEMERS, HPJ [1 ]
机构
[1] UNIV NIJMEGEN,DEPT BIOCHEM,6500 HB NIJMEGEN,NETHERLANDS
关键词
D O I
10.1093/nar/23.7.1119
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
By in vivo DMS footprint and reporter gene analyses we identified two transcription factor binding sites in the human c-sis/PDGF B gene promoter, The low basal activity of the PDGF B promoter in HeLa and undifferentiated K562 cells, which express low PDGF B mRNA levels, and in PC3 cells, which express a high PDGF B mRNA level, results from binding of a weak transcriptional activator between positions -64 and -61 relative to the transcription start site, Cytotrophoblast-tike JEG-3 cells, which do not express the 3.5 kb PDGF B mRNA, contain a transcriptional activator directed at the -64/-61 sequence, but DNA methylation may render the endogenous promoter inaccessible to this activator. A CCACCCAC element at position -61/-54 was identified as the in vivo binding site for a strong transcriptional activator in phorbol ester-treated megakaryocytic K562 cells, which express a high PDGF B mRNA level, Primary human fibroblasts, which do not transcribe the PDGF B gene, contain a transcriptional activator that recognizes an element between positions -60 and -45 but does not bind to the endogenous unmethylated promoter. Our results show that the complex expression pattern of the human PDGF B gene involves the cell type-specific expression of weak and strong transcriptional activators and regulation of promoter accessibility to these factors.
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页码:1119 / 1126
页数:8
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