Anomalous behaviour of the STAT3 binding site in the human c-myc P2 promoter.
The Signal Transducer and Activator of Transcription 3 (STAT3) is necessary for ES cell renewal, plays critical roles during vertebrate development, and has oncogenic potential. STAT3 also mediates cytokine responses notably in the induction of acute phase response genes in the liver. Thus STAT3 is a pleiotropic regulator during cell proliferation and a cell-specific mediator of pro-inflammatory responses. How STAT3 fulfils both roles is unclear. To address this question we attempted to characterise pre-initiation complexes (PICs) on STAT3-responsive promoters containing the c-myc P2 promoter element (P2E) or c-fos Serum-Inducible Element (SIE). Although both promoters mediated cytokine responses in HepG2 cells, poor binding of STAT1 and STAT3 in vitro precluded isolation of active promoter complexes on the P2E. The inability of STAT3 to bind the P2E in vitro correlated with failure of the P2E to mediate cytokine-responsive gene expression in several other cell types. Thus the c-myc P2E behaves as a dual-purpose STAT3 element with anomalous characteristics in HepG2 cells.
Vougier
Stéphanie
S
Centre for Biochemistry and Cell Biology, School of Biomedical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Cheung
Shing-Hu
SH
Li
Li
L
Hodgson
Glenn
G
Shaw
Peter E
PE
D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C116115:MYCBP protein, human; D050796:STAT3 Transcription Factor; D014157:Transcription Factors