A developmentally regulated octamer-binding activity in embryonal carcinoma cells which represses beta-interferon expression.
We have previously described ECIF-1, a DNA-binding factor present in nuclear extracts of murine embryonal carcinoma cells which specifically recognizes a region within the human beta-interferon promoter. We show that the promoter region located between -112 and -93 is sufficient for this binding activity, which is not due to binding of interferon-regulatory factor 1 or 2. By mutational analysis of the ECIF-1 site, it was determined that the central nucleotides which are critical for binding contain an octameric motif: ATTTACAT. The binding activity of ECIF-1 with its cognate site within the beta-interferon promoter decreases upon differentiation concurrently with the onset of interferon inducibility. Furthermore, by using an in vitro transcription assay with deleted promoter elements of the beta-interferon gene, we show that undifferentiated P19 nuclear extracts contain a repressing activity which depends on the presence of the ECIF-1 site. This repression is not observed using nuclear extracts from differentiated P19 cells. Comparison of the binding activity of this octamer site with others previously shown to be active in embryonal carcinoma cells reveals similarities and differences in the spectrum of proteins binding there.
Haggarty
A
A
Institut du Cancer de Montréal, Quebec, Canada.
Camato
R
R
Paterno
G
G
Cohen
L
L
Hiscott
J
J
Skup
D
D
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D051863:Host Cell Factor C1; D016899:Interferon-beta / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D050811:Octamer Transcription Factor-1; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494166:Pou2f1 protein, mouse; D014157:Transcription Factors; D016899:Interferon-beta