In vivo footprinting and functional analysis of the human c-sis/PDGF B gene promoter provides evidence for two binding sites for transcriptional activators.

Abstract:

: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-like 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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Dirks RP,Jansen HJ,van Gerven B,Onnekink C,Bloemers HP

doi

10.1093/nar/23.7.1119

subject

Has Abstract

pub_date

1995-04-11 00:00:00

pages

1119-26

issue

7

eissn

0305-1048

issn

1362-4962

pii

5w0012

journal_volume

23

pub_type

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